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Park, Haeng Ran,Kim, Se‐,Heon,Lee, Sei Young,Sung, Ji Min,Park, Ae Ran,Kang, Suki,Kim, Baek Gil,Choi, Yoon Pyo,Kim, Yong‐,Bae,Cho, Nam Hoon Wiley Subscription Services, Inc., A Wiley Company 2011 Cancer Vol.117 No.9
<P><B>Abstract</B></P><P><B>BACKGROUND:</B></P><P>Although radiation resistance is a primary issue in radiation therapy, attempts to find predictors of radiation resistance have met with little success. The authors therefore aimed to determine predictors for radiation resistance to improve the prognosis of head and neck squamous cell carcinoma (HNSCC).</P><P><B>METHODS:</B></P><P>HNSCC cell lines, SCC15, SCC25, and QLL1, irradiated with an acute dose of 4 grays (Gy) (RR‐4), a cumulative dose of 60 Gy (RR‐60), and a booster dose of 4 Gy over 60 Gy (RR‐60 + 4), were used with nonirradiated cell lines. Those were used in cDNA microarray, proteomics, Western blotting, and immunofluorescence, respectively. One hundred five HNSCC tissue samples with radiation resistance were analyzed by immunohistochemistry.</P><P><B>RESULTS:</B></P><P>Western blot analysis of RR‐60 cell lines was identical to the data of Nm23‐H1 overexpression by cDNA array and proteomic screening. Immunofluorescence demonstrated significant nuclear translocation of Nm23‐H1 in RR‐4 and RR‐60 cell lines, and less but still intense nuclear shuttling in RR‐60 + 4. Similarly, Nm23‐H1 nuclear localization was observed in 20% (21 of 105) of tissue samples. Univariate analysis demonstrated that Nm23‐H1 nuclear localization was strongly associated with overall and recurrence‐free survival. Multivariate stepwise Cox regression analysis showed that Nm23‐H1 nuclear localization (odds ratio [OR], 7.48) and N stage (OR, 2.13) were associated with overall survival, and Nm23‐H1 nuclear localization (OR, 3.02), T stage (OR, 1.43), and insufficient tumor margin (OR, 3.27) were associated with recurrence‐free survival.</P><P><B>CONCLUSIONS:</B></P><P>Overexpression of Nm23‐H1, specifically its nuclear translocation, may be a powerful predictor of radiation resistance in HNSCC. Cancer 2011. © 2010 American Cancer Society.</P>
Simple and Novel Assay of the Host-Guest Complexation of Homocysteine with Cucurbit[7]uril
( Se-ho Park ),( Jae-yeul Lee ),( Hyun-nam Cho ),( Kyoung-ran Kim ),( Seun-ah Yang ),( Hee-joon Kim ),( Kwang-hwan Jhee ) 한국미생물 · 생명공학회 2019 Journal of microbiology and biotechnology Vol.29 No.1
This paper introduces three ways to determine host-guest complexation of cucurbit[7]uril (CB[7]) with homocysteine (Hcy). After preincubating Hcy and cysteine (Cys) with CB[7], Ellman’s reagent (DTNB) was used to detect Hcy and Cys. Only Cys reacted with DTNB and Hcy gave a retarded color change. This suggests that the -SH group of Hcy is buried inside CB[7]. Human cystathionine γ-lyase (hCGL) decreased the level of Hcy degradation after preincubating Hcy and CB[7]. These results suggest that the amount of free Hcy available was decreased by the formation of a Hcy-CB[7] complex. The immunological signal of anti-Hcy monoclonal antibody was decreased significantly by preincubating CB[7] with Hcy. The ELISA results also show that ethanethiol group (-CH2CH2SH) of Hcy, which is an epitope of anti-Hcy monoclonal antibody, was blocked by the cavity in CB[7]. Overall, CB[7] can act as a host by binding selectively with Hcy, but not Cys. The calculated half-complexation formation concentration of CB[7] was 58.2 nmol using Ellman’s protocol, 97.9 nmol using hCGL assay and 87.7 nmol using monoclonal antibody. The differing binding abilities of Hcy and Cys towards the CB[7] host may offer a simple and useful method for determining the Hcy concentration in plasma or serum.
Salivary Mucocele with Osseous Metaplasia in a Dog
PARK, Jin-Kyu,HAN, Jung-Youn,HONG, Il-Hwa,HWANG, Ok-Kyung,HONG, Kyung-Sook,JI, Ae-Ri,KI, Mi-Ran,PARK, Se-Il,KIM, Tae-Hwan,CHOI, Dong-Hag,JEONG, Kyu-Shik Japanese Society of Veterinary Science 2009 The Journal of veterinary medical science Vol.71 No.7
<P>A 4-year-old, male, dachshund was referred to a certain local veterinary hospital because of a soft and fluctuant swelling in the left upper cervical region. The swelling was surgically removed and appeared to be filled with bloody mucus. Grossly, the swelling was identified as salivary mucocele and showed small multifocal whitish ossified tissue on its surface. Microscopically, the wall of salivary mucocele appeared as granulation tissue surrounding mucin, which was composed of loose edematous and vascularized connective tissue containing chronic inflammatory cells such as lymphocytes, plasma cells and macrophages. Characteristically, present case had ossifying components formed by metaplastic spindle cells in the wall of salivary mucocele. Therefore, the present case was diagnosed as salivary mucocele with osseous metaplasia in a dog.</P>
UVB를 조사한 HaCaT 세포의 세포사멸과 p53 및 GADD45 유전자 발현에 대한 파프리카 추출물 및 성분들의 효과
Se Eun Ha(하세은),Hyung-Do Kim(김형도),Jea Ran Kang(강제란),Jong Kun Park(박종군) 한국생명과학회 2011 생명과학회지 Vol.21 No.5
본 연구는 파프리카 추출물과 그 성분인 비타민 C, 라이코펜과 베타-카로틴이 UVB (ultraviolet-B)에 의한 유전독성의 감소에 효과를 보이는 지를 HaCaT 세포를 이용하여 분석하였다. 자외선을 조사하지 않은 정상 세포의 세포활성은 파프리카 추출물을 경우 처리하지 않은 대조군과 차이를 나타내지 않았지만 비타민 C의 경우 농도 의존적으로 증가시키는 것을 관찰하였다. 그러나 라이코펜과 베타-카로틴의 경우 농도 의존적으로 점차 세포활성이 감소하는 것으로 관찰되었다. UVB로 상해받은 세포를 추출물이나 그 성분으로 후 배양할 경우 정상 배양액으로 배양한 대조군에 비해 파프리카 추출물과 비타민C은 농도 의존적으로 세포 활성을 증가시켰으나 라이코펜과 베타-카로틴의 경우 농도 의존적으로 감소키는 것을 관찰할 수 있었다. 자외선을 조사하지 않은 정상세포의 핵 분절율은 파프리카 추출물과 비타민 C의 경우 대조군과 유의적인 차이를 나타내지 않았지만, 라이코펜, 베타-카로틴의 경우 농도 의존적으로 핵 분절율이 증가하는 것을 관찰하였다. UVB를 조사한 후 파프리카 추출물이나 비타민 C를 처리한 경우 정상 배양액으로 배양한 대조군에 비해 핵 분절율을 감소시켰지만 라이코펜과 베타-카로틴의 경우 농도 의존적으로 증가시켰다. 세포 상해에 반응하는 유전자인 p53과 GADD45의 단백질 수준을 Western blot으로 분석한 결과, 파프리카 추출물만 처리했을 경우 p53과 GADD45 단백질 수준은 처리하지 않은 대조군과 비교해서 유의미한 차이를 나타내지 않았으나 UVB를 조사한 후 파프리카 추출물을 처리한 경우 농도 의존적으로 p53 단백질 발현량이 감소하였다. 비타민 C를 단독 처리할 경우 대조군에 비해 p53과 GADD45 단백질 발현량은 감소하였으며, UVB를 조사한 후 비타민 C를 처리한 경우에도 농도 의존적으로 p53과 GADD45 단백질 발현량이 감소하는 것을 확인할 수 있었다. 그러나 라이코펜과 베타-카로틴만 단독 처리할 경우 p53과 GADD45 단백질 발현량이 처리하지 않은 대조군에 비해 농도 의존적으로 증가하였다. UVB를 조사한 후 베타-카로틴을 처리한 경우에도 상대적인 고농도에서 p53과 GADD45 단백질 발현량이 증가하는 것을 확인할 수 있었다. 위의 결과를 토대로 파프리카 추출물과 비타민 C는 UVB에 의해 손상된 세포의 세포 독성을 회복하는 효능이 있다고 생각된다. 라이코펜과 베타-카로틴의 경우에는 UVB에 의해 발현된 p53 단백질의 수준이 농도 의존적으로 더욱 증가하는 것으로 보아 UVB에 의한 세포고사가 라이코펜과 베타-카로틴에 의해 강화되는 것으로 생각된다. In the present study, the effects of paprika extract and its components including vitamin C, lycopene and beta-carotene on cell death in ultraviolet B (UVB)-exposed HaCaT cells were investigated. The cell viability upon treatment for 24 hr with either paprika extract or vitamin C alone was similar to or greater than that of the untreated control. However, the viability of the cells treated with lycopene or beta-carotene decreased to about 20% of that in the untreated control. When UVB-exposed cells were post-incubated for 24 hr in medium containing paprika extract or vitamin C, cell viability increased in a concentration dependent manner as compared to those post-incubated in a normal growth medium. In contrast, post-incubation of UVB-exposed cells with lycopene or beta-carotene decreased cell viability in a concentration dependent manner as compared to those post-incubated in a normal growth medium. The nuclear fragmentation analysis showed that paprika extract or vitamin C decreases UVB-induced apoptosis. The apoptotic nuclear fragmentation resulting from UVB exposure was also protected by the paprika extract or vitamin C post-incubation. However, the UVB-induced apoptotic nuclear fragmentation of the cells treated with lycopene or beta-carotene increased in a concentration dependent manner. Western blot analysis showed that either paprika extract or vitamin C treatment alone did not significantly change the level of p53 and GADD45 protein. Interestingly, post-incubation of UVB-exposed cells with paprika extract or vitamin C decreased the p53 and GADD45 protein level as compared to those post-incubated in a normal growth medium. In contrast, incubation of UVB-exposed or non-irradiated cells with lycopene or beta-carotene increased the p53 and GADD45 protein levels in a concentration dependent manner as compared to those incubated in a normal growth medium. All these results suggest that paprika extract and vitamin C help the survival of the UVB-exposed cells, while lycopene and beta-carotene potentiate the apoptotic death of UVB-exposed cells, in accordance with the respective changes in p53 and GADD45 protein levels.
FOXM1 mediates Dox resistance in breast cancer by enhancing DNA repair
Park, Yun-Yong,Jung, Sung Yun,Jennings, Nicholas B,Rodriguez-Aguayo, Cristian,Peng, Guang,Lee, Se-Ran,Kim, Sang Bae,Kim, Kyounghyun,Leem, Sun-Hee,Lin, Shiaw-Yih,Lopez-Berestein, Gabriel,Sood, Anil K,L Oxford University Press 2012 Carcinogenesis Vol.33 No.10
<B>Abstract</B><P>Transcription factors are direct effectors of altered signaling pathways in cancer and frequently determine clinical outcomes in cancer patients. To uncover new transcription factors that would determine clinical outcomes in breast cancer, we systematically analyzed gene expression data from breast cancer patients. Our results revealed that Forkhead box protein M1 (FOXM1) is the top-ranked survival-associated transcription factor in patients with triple-negative breast cancer. Surprisingly, silencing FOXM1 expression led breast cancer cells to become more sensitive to doxorubicin (Dox). We found that FOXM1-dependent resistance to Dox is mediated by regulating DNA repair genes. We further demonstrated that NFκB1 interacts with FOXM1 in the presence of Dox to protect breast cancer cells from DNA damage. Finally, silencing FOXM1 expression in breast cancer cells in a mouse xenograft model significantly sensitized the cells to Dox. Our systematic approaches identified an unexpected role of FOXM1 in Dox resistance by regulating DNA repair genes, and our findings provide mechanistic insights into how FOXM1 mediates resistance to Dox and evidence that FOXM1 may be a promising therapeutic target for sensitizing breast cancer cells to Dox.</P>