1,720,973 research outputs found
Antitumor Effect of Low-Dose of Rapamycin in a Transgenic Mouse Model of Liver Cancer
No full textPURPOSE: We investigate whether low-dose rapamycin is effective in preventing hepatocellular carcinoma (HCC) growth and treating HCC after tumor development in transgenic mice. MATERIALS AND METHODS: We established transgenic mice with HCC induced by activated HrasG12V and p53 suppression. Transgenic mice were randomly assigned to five experimental groups: negative control, positive control, tacrolimus only, rapamycin only, and tacrolimus plus rapamycin. The mice were further divided into two groups according to time to commencement of immunosuppressant treatment: de novo treatment and post-tumor development. RESULTS: In the de novo treatment group, marked suppression of tumor growth was observed in the rapamycin only group. In the post-tumor development group, the rapamycin only group displayed no significant suppression of tumor growth, compared to the positive control group. In T lymphocyte subset analysis, the numbers of CD4(+) effector T cells and CD4(+) regulatory T cells were significantly lower in the positive control, tacrolimus only, and tacrolimus plus rapamycin groups than the negative control group. Immunohistochemical analysis revealed significantly higher expression of phosphorylated-mTOR, 4E-BP1, and S6K1 in the positive control group than in the rapamycin only group. CONCLUSION: Low-dose rapamycin might be effective to prevent HCC growth, but may be ineffective as a treatment option after HCC development
Oxidation behavior and passivation mechanism of the T2 phase in Mo-Si-B alloys
No full textThe oxidation behavior of Mo5SiB2 (T2) phase was studied at 400-900 degrees C to examine their passivation mechanism which is critical for oxidation resistance in high temperature Mo-Si-B alloys. The oxide layer formation behavior of T2-rich Mo-Si-B alloy prepared by mechanical alloying was characterized using X-ray diffraction, scanning electron microscopy, and atom probe tomography. The results revealed that no effective passivation layer is formed and continuous B loss occurred before thermal oxidation of Si. Efficient passivation borosilicate layer can be formed above 900 degrees C, which further hinders oxygen penetration into the metal substrate and mass loss even for the temperature high enough for MoO3 volatilization. Si and B content profile in different oxidation temperatures showed that passivation layer formation attributed to the Si diffusion and oxidation towards Bdepleted surface region. It is suggested that T2 phase is crucial for effective oxidation resistance property of Mo-Si-B alloys.
만성 B형 간염 바이러스성 간질환에서 큰 간세포 이형성의 의의
No full textDept. of Medicine/박사[한글]
간세포 이형성은 육안적으로 확인할 수 없는 1mm 이하의 크기의 병변으로 뚜렷한 결절을 형성하지 않으며 작은 간세포 이형성 (small liver cell dysplasia; SLCD)와 큰 간세포 이형성 (large liver cell dysplasia; LLCD)으로 분류할 수 있다. SLCD는 전암병변으로서 어느 정도 개념이 정립되어 있으나, LLCD의 경우는 단순한 반응성 변화인지, 또는 간세포암종 발생과 밀접한 연관이 있는 전암병변인지 아직 의견의 일치가 없다. 본 연구에서는 LLCD의 유전생물학적 특성에 대하여 살펴보고 LLCD의 전암병변으로서의 의의를 밝히는 것이 목적이다.
외과적으로 절제한 만성 B형 간염 바이러스성 간경변 34 증례를 대상으로 연구를 시행하였으며 LLCD 31증례, SLCD 19증례 및 HCC 21증례가 포함되었다. 세포주기조절인자인 p21, p27, p16, Tp53, DNA 손상 표지자인 γ-H2AX에 대한 면역조직화학염색을 시행하였고, 세포역동성을 알아보기 위하여 세포증식능 표지자 PCNA와 Ki-67 발현율 및 세포고사의 빈도를 측정하였다. 또한 Feulgen 방법으로 미세핵의 빈도를 구하여 염색체 불안정성의 정도를 살펴보았고, 정량적인 형광제자리부합화 방법으로 각 병변세포의 텔로미어 길이를 측정하였으며, senescence-associated β-galactosidase (SA-β-Gal) 염색으로 세포노화 여부를 판단하였다.
이형성이 없는 간세포, LLCD, SLCD 및 간세포암종의 순서로 세포주기조절인자 (p21, p27, p16, p53)의 소실의 정도가 높았고, γ-H2AX 병소 및 미세핵의 빈도도 점점 증가하는 양상을 보였다. PCNA, Ki-67 및 TUNEL labeling index로 알아본 net cellular gain도 이형성이 없는 간세포, LLCD, SLCD, 간세포암종 순으로 높아졌으며, 텔로미어 길이는 점점 짧아졌고, SA-β-Gal 염색상 간경변에서는 노화된 세포가 많이 관찰되었으나, LLCD 및 SLCD에서는 관찰되지 않았다. 따라서 LLCD는 노화성 병변보다는 증식성 병변일 가능성이 더 높을 것으로 판단되며, 세포주기조절인자의 비활성화, 텔로미어 길이의 감소, DNA 손상 및 염색체 불안정성의 증가를 보이는 병변으로 간암발생과 밀접한 연관이 있는 전암병변일 가능성을 본 연구에서 제시하고자 한다.
[영문]
Liver cell dysplasia or dysplastic foci are defined as microscopic lesions measuring less than 1mm in diameter which do not form circumscribed nodules, and are often found in chronic liver disease. These lesions have been classified into two types: large liver cell dysplasia (LLCD) and small liver cell dysplasia (SLCD). Although SLCD has been more or less established as a precursor to hepatocellular carcinoma (HCC), the significance of LLCD is still controversial - while some have favored a reactive/degenerative nature for the lesion, there is increasing evidence that it may actually be related to hepatocarcinogenesis. A comprehensive analysis of LLCD was performed in this study, evaluating the cell cycle dynamics, proliferation and apoptosis, DNA damage and senescence. The molecular features - including senescence, cell cycle checkpoint status, DNA damage and chromosomal instability - and cell dynamics of LLCD in HBV-related cirrhotic livers were explored to further characterize the nature of LLCD.
Thirty-four formalin-fixed specimens and 19 fresh frozen liver specimens were obtained from surgically resected cases of HBV-related cirrhosis and examined for the presence of LLCD, SLCD and HCC. The immunohistochemical expression of p21, p27, p16, Tp53, PCNA, Ki-67 and γ-H2AX, telomere lengths, apoptotic activity, micronuclei index and senescence-associated β-galactosidase (SA-β-Gal) activity were examined for each lesion.
The p21, p27 and p16 cell cycle checkpoint markers - which were expressed at low levels in normal hepatocytes - were activated in cirrhosis but were diminished gradually from LLCD through SLCD to HCC, along with an increase in Tp53 expression. Significant shortening of telomere length was seen in non-dysplastic hepatocytes compared to normal liver, and in LLCD compared to non-dysplastic hepatocytes. There was a general decrease in telomere length from non-dysplastic hepatocytes, LLCD, SLCD to HCC. The accumulation of γ-H2AX foci and the micronuclei index were extremely low in normal hepatocytes and there was a significant gradual increase from non-dysplastic hepatocytes, LLCD, SLCD to HCC. An increase in net cellular gain (high proliferative activity and low apoptotic index) from normal hepatocytes, non-dysplastic hepatocytes, LLCD, SLCD to HCC was seen. The SA-β-Gal activity was weaker and less frequent in LLCD compared to the periseptally located non-dysplastic hepatocytes.
The increase in net cellular gain and the weak SA-β-Gal activity in LLCD suggest that LLCD may represent a proliferative lesion rather than a population of terminally differentiated end-stage hepatocytes. The loss of cell cycle checkpoint markers in LLCD may allow clonal expansion of hepatocytes with dysfunctional, shortened telomeres, and accumulation of DNA damage and chromosomal instability.ope
원발성 ‘중간형’ (간세포-담관상피세포) 간암종
No full textDept. of Medical Science/석사[한글]
원발성 간암종은 일반적으로 각각 간세포나 전구 간세포,그리고 담관 상피세포에서 기원하는 간세포암종과 담관상피암종으로 분류한다. 그외에 혼합 간세포-담관상피암종이 보고된 바 있으며, 이러한 암종의 기원세포로는 난원 모양이 전구세포의 가능성이 제시되고 있다.이러한 난원 모양의 전구세포는 간세포와 담관상피세포로 모두 분화할
수 있는 이중분화능력을 가진 세포로 알려졌다. 본 연구에서는 간세포암종과 담관상피 암종의 중간형태를 보이는 '중간형'의 원발성 간암종을 대상으로 간세포 표지자(alpha-fetoprotein, hepatocyte), 담관상피세포 표지자 (carcinoembryonic antigen,cytokeratin 19) 및 전구세포(progenitor cell) 표지자(c-kit)에 대한 면역조직화학염색
을 시행하여 이러한 '중간형'(간세포-담관상피세포) 간암종이 간에 존재하는 전구세포에서 기원하는 것을 밝히고자 하였다.
총 48 예의 원발성 간암종을 연구대상으로 하였으며, 이중 10 예는 '중간형'(간세포- 담관상피세포)간암종으로 치밀한 섬유조직으로 둘러싸여 있으면서 코드상 배열을 취하고 있는 작고 크기가 일정한 둥근 또는 난원형 종양세포들로 이루어져 있었으며,종양세포들은 세포질이 적으면서 과염색성의 핵을 갖고 있었다. 또한 4 예는 혼합
간세포-담관상피암종의'이행성'아형으로 분류하였다. 9예는 형태학적으로는 거의 전형적인 간세포암종의 소견을 보였으나, 좀더 작은 세포들로 이루어져 있었고 이들은 소세포성 간세포암종으로 분류하였다. 나머지 24 예는 20 예의 전형적인 간세포암종과 4 예의
전형적인 담관상피암종으로 분류하였다.면역조직화학적 염색을 시행한 결과,10 예의'중간형' (간세포-담관상피세포) 암종 중 6 예에서는 간세포 및 담관상피세포 표지자가 동시에 발현되었으며, 6 예는 c-kit염색에 양성을 나타냈다.4 예의 '이행성' 혼합 간세포-담관상피암종 중에서는 2 예가 간세포와 담관상피세포으 표지자를
동시에 발현하였고, 이 2 예 중에서 1예에서 c-kit를 발현하였다.소세포성 간세포암종 중 3 예에서 간세포와 담관상피세포의 표지자가 모두 양성이었으나 c-kit를 발현하는
예는 없었으며,나머지 6 예에서는 모두 c-kit를 발현하였으나 담관상피세포 표지자를 발현하는 예는 없었다.전형적인 간세포암종은 모두 간세포 표지자만 발현하였으며,전형적인 담관상피암종은 모두 담관상피세포 표지자만 발현하였다.
이상의 결과로 '중간형'(간세포-담관상피세포)간암종은 간세포와 담관상피세포로의 이중분화능력을 갖는 전구세포로부터 기원한 간암종으로 특별한 아형을 생각된다.
[영문]
There is increasing evidence of 'oval-like' hepatic progenitor cell in human liver disease. It is a matter of debate whether primary liver carcinoma with 'intermediate'(hepatocyte-biliary epithelial cell) phenotype arises from transformed progenitor cells with the biopotential to differentiate into hepatocytes and biliary epithelial cells. In this study, primary liver carcinomas with intermediate features were identified and an
immunohistochemical analysis was performed using hepatocytic markers (alpha-fetoprotein and hepatocyte), biliary epithelial cell markers (carcinoembryonic antigen and cytokeratin 19) and progenitor cell marker (c-kit), in order to study the orgin of primary 'intermediate' carcinomas.
Forty-seven cases of primary liver carcinomas were the subject of study, and ten of these cases demonstrated strands or trabeculae of small,uniform, round to oval cells with scanty cytoplasm and hyperchoromatic nuclei embedded within a thick desmoplastic stroma, and hence named 'intermediate'(hepatocyte-
biliary epithelial cell) carcinomas. Four cases were designated transitional type CHC. Nine were named HCC, small cell type, demonstrating morphological features almost compatible with typical HCCs except that they were composed of smaller cells. The remaining cases consisted of 20 typical HCCs and
4typical CCs. Six of 10 'intermediate' carcinomas showed simultaneous expression of hepatocytic(AFP or hepatocyte) and biliary (CEA or CK19) markers and six showed positive immunohistochemistry for c-kit. Of the 4 cases of
transitional CHCs, two expressed both hepatocytic and biliary markers, and one of these 2 cases ws positive for c-kit. Three cases of HCC,small cell type were positive for both hepatocytic and biliary markers but none expressed c-kit and the other 6 cases demonstrated expression of c-kit but were negative
for biliary markers. The 20 typical HCCs expressed only hepatocytic markers and the 4 typical CCs expressed only biliary markers.
From these results it can be suggested that 'intermediate'(hepatocyte-biliary epithelial cell) carcinoma is a distint type of primary liver carcinoma orginating from transformed hepatic progenitor cells that have the biopotential
to differentiate into both hepatocytic and biliary lineage.ope
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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