• 한국수정란이식학회지
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• 제30권3호
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• pp.249-255
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• 2015

Diabetes mellitus, the most common metabolic disorder, is divided into two types: type 1 and type 2. The essential treatment of type 1 diabetes, caused by immune-mediated destruction of ${\beta}-cells$, is transplantation of the pancreas; however, this treatment is limited by issues such as the lack of donors for islet transplantation and immune rejection. As an alternative approach, stem cell therapy has been used as a new tool. The present study revealed that bone marrowderived mesenchymal stromal cells (BM-MSCs) could be transdifferentiated into pancreatic cells by the insertion of a key gene for embryonic development of the pancreas, the pancreatic and duodenal homeobox factor 1 (PDX1). To avoid immune rejection associated with xenotransplantation and to develop a new cell-based treatment, BM-MSCs from ${\alpha}$-1,3-galactosyltransferase knockout (GalT KO) pigs were used as the source of the cells. Transfection of the EGFP-hPDX1 gene into GalT KO pig-derived BM-MSCs was performed by electroporation. Cells were evaluated for hPDX1 expression by immunofluorescence and RT-PCR. Transdifferentiation into pancreatic cells was confirmed by morphological transformation, immunofluorescence, and endogenous pPDX1 gene expression. At 3~4 weeks after transduction, cell morphology changed from spindle-like shape to round shape, similar to that observed in cuboidal epithelium expressing EGFP. Results of RT-PCR confirmed the expression of both exogenous hPDX1 and endogenous pPDX1. Therefore, GalT KO pig-derived BM-MSCs transdifferentiated into pancreatic cells by transfection of hPDX1. The present results are indicative of the therapeutic potential of PDX1-expressing GalT KO pig-derived BM-MSCs in ${\beta}-cell$ replacement. This potential needs to be explored further by using in vivo studies to confirm these findings.

• Genomics & Informatics
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• 제18권1호
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• pp.3.1-3.8
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• 2020

Patient-derived xenograft (PDX) mouse models are frequently used to test the drug efficacy in diverse types of cancer. They are known to recapitulate the patient characteristics faithfully, but a systematic survey with a large number of cases is yet missing in lung cancer. Here we report the comparison of genomic characters between mouse and patient tumor tissues in lung cancer based on exome sequencing data. We established PDX mouse models for 132 lung cancer patients and performed whole exome sequencing for trio samples of tumor-normal-xenograft tissues. Then we computed the somatic mutations and copy number variations, which were used to compare the PDX and patient tumor tissues. Genomic and histological conclusions for validity of PDX models agreed in most cases, but we observed eight (~7%) discordant cases. We further examined the changes in mutations and copy number alterations in PDX model production and passage processes, which highlighted the clonal evolution in PDX mouse models. Our study shows that the genomic characterization plays complementary roles to the histological examination in cancer studies utilizing PDX mouse models.

• Genomics & Informatics
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• 제18권1호
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• pp.6.1-6.9
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• 2020

Acute leukemia represents the most common pediatric malignancy comprising diverse subtypes with varying prognosis and treatment outcomes. New and targeted treatment options are warranted for this disease. Patient-derived xenograft (PDX) models are increasingly being used for preclinical testing of novel treatment modalities. A novel approach involving targeted error-corrected RNA sequencing using ArcherDX HemeV2 kit was employed to compare 25 primary pediatric acute leukemia samples and their corresponding PDX samples. A comparison of the primary samples and PDX samples revealed a high concordance between single nucleotide variants and gene fusions whereas other complex structural variants were not as consistent. The presence of gene fusions representing the major driver mutations at similar allelic frequencies in PDX samples compared to primary samples and over multiple passages confirms the utility of PDX models for preclinical drug testing. Characterization and tracking of these novel cryptic fusions and exonal variants in PDX models is critical in assessing response to potential new therapies.

• 치위생과학회지
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• 제23권4호
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• pp.343-350
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• 2023

Background: Digital panoramic dental X-ray equipment (PDX) is frequently used by patients and dental workers for diagnosis and examination in dental institutions; however, infection control has not been properly implemented. Therefore, in this study, we aimed to systematically review the potential risk of cross-infection in the dental environment by investigating the contamination level of general aerobic bacteria and Staphylococcus aureus, which are important in hospital infections, in PDX areas that people mainly contact. Methods: This survey was conducted from March to May 2023 and covered one general hospital, three dental hospitals, and nine dental clinics equipped with PDX. Bacteria samples were collected from the left-handle, right-handle, forehead support, and head side support as the patient's contact areas, as well as the X-ray exposure switch and left-click mouse button as the dental hygienist's contact areas of the PDX. The collected bacteria were spread on Petrifilm, and colonies formed after 48 hours of culture were counted. Results: General aerobic bacteria and S. aureus were detected in all areas investigated. Significant differences in bacterial counts between different regions of the PDX were observed in both groups (p<0.001). The detection rates of general aerobic bacteria (p<0.001) and S. aureus (p<0.001) were significantly higher in the contact areas of patients than those of dental hygienists. A positive correlation was observed between the forehead and the temple region in terms of general aerobic bacteria and S. aureus detection (r=1) (p<0.01). Conclusion: Taken together, the presence of many bacteria, including S. aureus, detected in PDX indicates that PDX has a potential cross-infection risk. Our results therefore highlight the need for the development of appropriate disinfection protocols for reusable medical devices such as PDX and periodic infection prevention training for hospital-related workers, including dental hygienists.

• 공업화학
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• 제16권4호
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• pp.581-587
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• 2005

생분해성 폴리머의 모노머로 사용가능한 파라디옥산온(p-dioxanone, 1,4-dioxan 2-one, PDX)을 고순도로 정제하기 위해, 용해도 실험을 통하여 불순물을 선택적으로 제거하기에 적절한 용매를 선정하였으며, 용매를 일부 포함한 부분 경막결정화 실험을 실시하였다. 용매로는 에틸아세테이트(EA), 데트라하이드로퓨란(THF), 아세톤(acetone), 메탄올(MeOH), 에탄올(EtOH), 1-프로탄올(PrOH), 1-부탄올(BtOH), 1-펜탄올(PtOH) 등을 사용하여 $-10{\sim}15^{\circ}C$의 온도범위에서 용해도 실험을 실시하였으며, 정규이론식에 의해 구한 활동도 계수를 포함한 비이상형 용해도식과 비교하였다. 그 결과, 용매에 따른 PDX의 용해도 및 용해도의 온도의존성은 상대적으로 용해도가 큰 용매(acetone, EA, THF)가 알코올계에 비해 크게 나타내었으며, 동일한 알코올계에서는 분자량이 작고 극성이 큰 용매일수록 큰 값을 나타내었다. 또한 에틸아세테이트를 사용한 부분 경막 결정화 시, 용매를 PDX에 비해 1:9(무게비)로 적게 사용한 경우에도 중합에 영향을 미치는 불순물이 선택적으로 제거되었으며, 99.9% 이상의 고순도 PDX를 얻을 수 있었다.

• Journal of Gastric Cancer
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• 제20권1호
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• pp.60-71
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• 2020

Purpose: The utility of 18-fluordesoxyglucose positron emission tomography ([¹⁸F]-FDG-PET) combined with computer tomography or magnetic resonance imaging (MRI) in gastric cancer remains controversial and a rationale for patient selection is desired. This study aims to establish a preclinical patient-derived xenograft (PDX) based [¹⁸F]-FDG-PET/MRI protocol for gastric cancer and compare different PDX models regarding tumor growth and FDG uptake. Materials and Methods: Female BALB/c nu/nu mice were implanted orthotopically and subcutaneously with gastric cancer PDX. [¹⁸F]-FDG-PET/MRI scanning protocol evaluation included different tumor sizes, FDG doses, scanning intervals, and organ-specific uptake. FDG avidity of similar PDX cases were compared between ortho- and heterotopic tumor implantation methods. Microscopic and immunohistochemical investigations were performed to confirm tumor growth and correlate the glycolysis markers glucose transporter 1 (GLUT1) and hexokinase 2 (HK2) with FDG uptake. Results: Organ-specific uptake analysis showed specific FDG avidity of the tumor tissue. Standard scanning protocol was determined to include 150 μCi FDG injection dose and scanning after one hour. Comparison of heterotopic and orthotopic implanted mice revealed a long growth interval for orthotopic models with a high uptake in similar PDX tissues. The H-score of GLUT1 and HK2 expression in tumor cells correlated with the measured maximal standardized uptake value values (GLUT1: Pearson r=0.743, P=0.009; HK2: Pearson r=0.605, P=0.049). Conclusions: This preclinical gastric cancer PDX based [¹⁸F]-FDG-PET/MRI protocol reveals tumor specific FDG uptake and shows correlation to glucose metabolic proteins. Our findings provide a PET/MRI PDX model that can be applicable for translational gastric cancer research.

• Molecules and Cells
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• 제41권12호
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• pp.1033-1044
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• 2018

As sessile organisms, plants have evolved to adjust their growth and development to environmental changes. It has been well documented that the crosstalk between different plant hormones plays important roles in the coordination of growth and development of the plant. Here, we describe a novel recessive mutant, mildly insensitive to ethylene (mine), which displayed insensitivity to the ethylene precursor, ACC (1-aminocyclopropane-1-carboxylic acid), in the root under the dark-grown conditions. By contrast, mine roots exhibited a normal growth response to exogenous IAA (indole-3-acetic acid). Thus, it appears that the growth responses of mine to ACC and IAA resemble those of weak ethylene insensitive (wei) mutants. To understand the molecular events underlying the crosstalk between ethylene and auxin in the root, we identified the MINE locus and found that the MINE gene encodes the pyridoxine 5′-phosphate (PNP)/pyridoxamine 5′-phosphate (PMP) oxidase, PDX3. Our results revealed that MINE/PDX3 likely plays a role in the conversion of the auxin precursor tryptophan to indole-3-pyruvic acid in the auxin biosynthesis pathway, in which TAA1 (TRYPTOPHAN AMINOTRANSFERASE OF ARABIDOPSIS 1) and its related genes (TRYPTOPHAN AMINOTRANSFERASE RELATED 1 and 2; TAR1 and TAR2) are involved. Considering that TAA1 and TARs belong to a subgroup of PLP (pyridoxal-5′-phosphate)-dependent enzymes, we propose that PLP produced by MINE/PDX3 acts as a cofactor in TAA1/TAR-dependent auxin biosynthesis induced by ethylene, which in turn influences the crosstalk between ethylene and auxin in the Arabidopsis root.

• 한국식품과학회지
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• 제39권6호
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• pp.701-707
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• 2007

민간요법에서 항당뇨 및 항비만 효과가 있는 것으로 알려진 길경의 항당뇨 효과가 있는 지 여부를 in vitro에서 조사하기 위해서 길경을 70% 에탄올로 추출한 후 메탄올과 물을 섞은 용액으로 단계별로 XAD-4 column으로 분획하였다. 본 연구에서는 1) 3T3-L1 섬유아세포와 지방세포에서 길경의 추출 분획물이 인슐린처럼 작용하는 인슐린성 물질이거나, 2) 인슐린 작용을 향상시키는 인슐린 민감성 물질이거나, 또는 3) 포도당 자극에 의한 인슐린 분비를 향상시키거나, 4) 베타세포의 기능과 양을 증가시키는데 관여하는 유전자인 IRS-2, glucokinase, PDX-1의 mRNA 발현을 향상시키거나, 5) $\alpha-glucoamylase$ 활성을 억제하는 물질로 작용하는 지 여부를 조사하였다. 길경 추출 분획물은 인슐린성 물질로 작용하지 않았다. 반면에 0, 20와 100%메탄올층은 3T3-L1 지방세포에서 인슐린 자극에 의한 포도당 흡수를 증가시켰다. 이 분획층 중에서 특히 0%과 100% 메탄올 분획층은 분화 유도물질의 작용을 향상시켜 3T3-L1 섬유아세포에서 지방세포로의 분화 및 중성 지방의 축적을 증가시켰다. 그러므로 이들은 $PPAR-{\gamma}$ agonist로 작용하는 물질을 함유할 가능성이 매우 높다. 인슐린을 분비하는 세포인 Min6 세포에서 포도당 자극에 의한 인슐린 분비를 향상시키는 지 여부를 조사하였는데 20, 80 그리고 100% 메탄올층은 포도당 자극에 의한 인슐린 분비를 증가시켰다. 그 기전은 인슐린 분비와 베타세포의 증식에 관여하는 유전자의 IRS-2, glucokinase 그리고 PDX-1의 mRNA의 양을 증가시키는 것과 관련이 있다. 결론적으로 길경은 지방 세포의 분화를 촉진하는 물질, 인슐린 민감성을 향상시키는 물질 그리고 베타세포의 기능과 증식을 촉진시키는 물질을 함유하고 있으므로 우리나라 및 아시아의 사람들에서 많이 유발되는 비만을 동반하지 않은 당뇨병 및 인슐린 저항성의 치료와 예방에 중요한 역할을 할 것으로 사료된다.

• Korean Chemical Engineering Research
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• 제43권5호
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• pp.595-602
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• 2005

파라디옥사논에 포함된 주요한 불순물인 디에틸렌글리콜을 제거하기 위해, 파라디옥사논과 디에틸렌글리콜과의 이성분계 고액 상평형 및 혼합물의 밀도를 측정하였으며, 종(seed)을 이용한 경막 용융결정화 실험을 하였다. 얻어진 2성분계 고액 상평형 결과는 단순 공융계를 형성하였는데, 공용점은 파라디옥사논의 0.08 몰농도에서 246 K였다. 또한, 혼합물의 밀도 데이터는 ${\rho}_l=k_1+k_2x+k_3T+k_4xT$ 식과 잘 연관되었으며, 각 파라메타인 $k_1$, $k_2$, $k_3$ 및 $k_4$의 값은 0.405, 1.361, 0.002, -0.004이었다. 용융결정화 실험에서 결정 성장속도(G)는 냉각속도가 감소하거나 파라디옥사논의 초기농도가 증가할수록 감소하는 경향을 나타내었으며, 결정 성장속도식은 과냉각 온도의 1.5승에 비례하였다. 또한, 불순물의 제거 정도를 나타내는 유효 분배계수($K_{eff}$)는 냉각속도 및 PDX 초기농도가 증가할수록 증가하는 경향을 나타내었으며, 유효분배계수는 Wintermantel 모델에 의해 $K_{eef}=-0.0604+6.392{\times}Z$ 관계로 표현되었다. 최종적으로 얻어진 PDX 순도는 결정화 조작변수를 최적화하여 99% 이상으로 조절할 수 있음을 알 수 있었다.

• 충청수학회지
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• 제31권2호
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• pp.231-237
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• 2018

Hardy's inequality is refined non-trivially as the form $${\int_{0}^{{\infty}}}\{{\frac{1}{x}}{\int_{0}^{x}}f(t)dt\}^pdx{\leq}Q_f{\times}({\frac{p}{p-1}})^p{\int_{0}^{x}}f^p(x)dx$$ for some $Q_f:0{\leq}Q_f{\leq}1$. $P{\acute{o}}lya$-Knopp's inequality is also refined by the similar form.