• Asian Pacific Journal of Cancer Prevention
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• 제15권24호
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• pp.10813-10817
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• 2015

Background: Possible roles of nestin expression in terms of predicting intravesical BCG therapy response in T1 high grade bladder cancer patients were investigated. Materials and Methods: T1 high grade bladder cancer patients who were treated with intravesical BCG between 1990-2009 were included. Immunohistochemical staining for nestin expression was performed. Nestin(+) and nestin(-) patients were compared in terms of recurrence and progression rates. Results: Sixty-three patients were included and median follow-up time was twenty-five months. After staining; 33 patients (52.4%) were classified as nestin (+) and 30 (47.6%) as (-). Nestin (+) patients were more likely to recur compared to nestin (-) patients (60.6% vs. 30%, p<0.05). Progression rates were also higher in nestin (+) patients, although this result did not reach statistical significance (15.2 % vs. 10 %, p=0.710). Conclusions: Nestin expression, which seems effective in predicting recurrence, appears to have a potential role in the urothelial carcinoma tumorigenesis. Patients with high grade bladder cancer and positive nestin expression need close follow-up and might be informed about more tendency to recur. Further comprehensive studies including larger patient cohorts may clarify the role of nestin in bladder cancer.

• 생명과학회지
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• 제16권4호
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• pp.589-597
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• 2006

본 연구에서는 T24 인체방광암 및 U937 백혈병 세포의 증식에 미치는 genistein의 영향을 조사 하였다. Genistein이 처리된 T24 및 U937 세포는 처리 농도 의존적으로 세포의 증식이 현저히 감소되었으며 심한 형태적 변형이 동반되었으나, U937 세포에서 보다 높은 감수성을 보였다. 이러한 T24 및 U937 세포의 증식억제 및 형태 변형은 G2/M기의 세포주기 억제 및 apoptosis 유발과 연관성이 있음을 flow cytometry를 이용한 세포주기의 분석을 통하여 확인하였다. T24 세포에서 genistein에 의한 G2/M arrest는 cyclin A, cyclin B1 및 Cdc25C 등의 단백질 발현 감소와 연관성이 있었으나, 종양억제 유전자 p53 및 Cdk inhibitor p21의 발현에는 큰 변화가 없었다. U937 세포에서 genistein에 의한 G2/M arrest는 cyclin B1 및 p53 비의존적인 p21의 발현 증가와 연관성이 있었다. 이상의 결과들은 현재까지 거의 연구가 진행된 바 없는 인체방광암 및 백혈병 세포에서 genistein의 항암작용을 이해하는데 중요한 자료가 될 것이고 나아가 genistein을 포함한 그와 유사한 항암제 후보물질들의 연구에 있어서 기초 자료로서 사용될 수 있을 것으로 생각된다.

• The Korean Journal of Physiology and Pharmacology
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• 제4권2호
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• pp.159-167
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• 2000

We have synthesized a novel platinum(II) coordination complex containing cis-1,2-diaminocyclohexane (DACH) as a carrier ligand and 1,2-dichloroethane (DCE) as a leaving group. In addition, nitrate was added to improve the water-solubility. A new series of [Pt(cis-DACH)(DCE)] $2NO_3(PC)$ was evaluated for its cytotoxic activity on T-24 and J-82 human bladder carcinoma cells and normal primary cultured kidney cells. PC has demonstrated high levels of cytotoxicity against T-24 and J-82 cells. The cytotoxicity of PC against rabbit proximal renal tubular cells, human renal cortical cells and human renal cortical tissues, determined using the MTT assaying technique, the $[^3H]-thymidine$ uptake and glucose consumption tests, was found to be quite less than those of cisplatin. Based on these results, this novel platinum(II) coordination complex appears to be better for improving antitumor activities with low nephrotoxicity and is a valuable lead in the development of new clinically available anticancer chemotherapeutic agents.

• 동의생리병리학회지
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• 제18권5호
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• pp.1449-1455
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• 2004

Bufonis venenum (dried toad venom; Chinese name, Chan su) is a traditional Chinese medicine obtained from the skin venom gland of the toad. It has long been used in treating arrhythmia and other heart diseases in China and other Asian countries. Additionally, Bufonis venenum has been reported to selectively inhibit the growth of various lines of human cancer cells. In the present study, it was examined the effects of extract of Bufonis venenum (EBV) on the growth of human bladder carcinoma cell line T24 in order to investigate the anti-proliferative mechanism and induction of apoptosis by EBV. Treatment of T24 cells to EBV resulted in the growth inhibition, morphological change and induction of apoptotic cell death in a dose-dependent manner. Flow cytometric analysis revealed that EBV treatment caused G2/M phase arrest of the cell cycle and down-regulation of cyclin A, cyclin B1 and Cdc2, which was associated with a marked up-regulation of cyclin-dependent kinases (Cdks) inhibitor p21 (WAF1/CIP1) in a p53-independent manner. The Cdc25C expression was also significantly inhibited by EBV treatment, however Wee1 kinase expression was not affected. The induction of apoptotic cell death by EBV was connected with down-regulation of anti-apoptotic Bcl-XS/L expression without alteration pro-apoptotic Bax expression. Taken together, these findings suggest that EBV may be a potential chemotherapeutic agent for the control of human bladder carcinorma cells and further studies will be needed to identify the active compounds that confer the anti-cancer activity of EBV.

• Asian Pacific Journal of Cancer Prevention
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• 제15권23호
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• pp.10401-10405
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• 2015

Background: Molecular prognostic markers have been under investigation for the last decade and no validated marker to date has been proven to be used in daily clinical practice for urinary bladder cancers. The aim of the present study is to evaluate the significance of HYAL-1 expression in prediction of recurrence and progression in pT1 urothelial carcinomas. Materials and Methods: Eighty-nine urothelial carcinoma cases staged as T1 according to 2004 WHO classification were studied. Representative sections from every case were stained immunohistochemically for HYAL-1 and scored between 0 and +3, according to staining density, and graded as low and high for the scores 0-1 and 2-3, respectively. Results: Of the 89 pT1 bladder cancer patients, HYAL-1 expression was high in 92.1% (82 patients; 72 patients +3 and 10 patients +2) and low in 7.9% (only 7 patients; 6 patients +1 and 1 patient 0) of the cases. Of the 89 patients, 38 (42.7%) had recurrence and 22 (24.7%) showed progression. HYAL-1 staining did not show significant characteristics for tumor grade, accompanying CIS, multiplicity, tumor size, age and sex. HYAL-1 expression did not have any prognostic value in estimating recurrence or progression. Conclusions: HYAL-1 expression was found to be high, but did not have any prognostic importance in T1 bladder urothelial carcinomas.

• The Korean Journal of Physiology and Pharmacology
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• 제7권2호
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• pp.111-117
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• 2003

Cisplatin is often effective in cancer treatment, but its clinical use is limited because of its nephrotoxicity. We have synthesized new platinum(II) coordination complexes (PC-1 & PC-2) containing trans-${\iota}$ and cis-1,2-diaminocyclohexane (DACH) as carrier ligands and L-3 -phenyllactic acid (PLA) as a leaving group with the aim of reducing nephrotoxicity but maintaining its anticancer activity. In this study, new platinum(II) complex compounds were evaluated for selective cytotoxicity on cancer cell-lines and normal kidney cells. The new platinum complexes have demonstrated high efficacy in the cytotoxicity against human bladder carcinoma cell-lines (T-24/HT-1376). The cytotoxicity of these compounds against rabbit proximal renal tubular cells and human renal cortical tissues, was determined by MTT assay, the [3H]-thymidine uptake and glucose consumption test, and found to be quite less than those of cisplatin. Based on our results, these novel platinum compounds appear to be valuable lead compounds with high efficacy and low nephrotoxicity.

• 생명과학회지
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• 제15권3호
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• pp.323-331
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• 2005

남미지역에서 자생하는 Tabebuia avellanedae라는 나무의 수피에서 동정된 quinone계 물질이며, DNA topoisomeras억제제로 알려진 $\beta-lapachone$의 항암작용에 관한 부가적인 자료를 얻기 위하여 인체 간암(HepG2) 및 방광암(T24)세포를 대상으로 조사한 결과 다음과 같은 결과를 얻게 되었다. MTT assay 및 flow cytometry 분석 등의 결과에서, $\beta-lapachone$의 처리에 따라 조사된 두 가지 암세포에서 $\beta-lapachone$처리 농도의존적으로 암세포의 심한 형태적 변형이 동반되면서 암세포의 증식이 억제되었으며, 생존율이 저하되었고 이는 apoptosis유발과 상관성이 있음을 알 수 있었다. $\beta-lapachone$처리에 의한 두 암세포의 증식억제는 종양억제 유전자 p53 및 Cdk inhibitor p21의 발현과는 큰 연관성이 없음을 RT-PCR 및 Western blot analysis를 통하여 확인하였다. 그러나 전사조절인자 Sp-1 및 세포증식 주요조절인자인 PCNA의 단백질 발현은 $\beta-lapachone$처리에 따라 매우 감소되었으며, telomere조절에 중요한 인자들의 선택적 발현 저하 현상도 관찰되었다. 이상의 결과들은 인체 암세포에서 $\beta-lapachone$의 항암작용을 이해하는 중요한 자료가 될 것이며, $\beta-lapachone$과 유사한 화학적 구조 및 성질을 가지는 항암제 후보물질들의 항암기전 비교 및 항암제 개발을 위한 기초 자료로서 응용될 것이다.

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.1957-1962
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• 2012

Bladder cancer is a common malignancy worldwide. Despite the increased use of cisplatin-based combination therapy, the outcomes for patients with advanced disease remain poor. Recently, altered activation of the PI3K/Akt/mTOR pathway has been associated with reduced patient survival and advanced stage of bladder cancer, making its upstream or downstream components attractive targets for therapeutic intervention. In the present study, we showed that treatment with DTCM-glutaramide, a piperidine that targets PDK1, results in reduced proliferation, diminished cell migration and G1 arrest in 5637 and T24 bladder carcinoma cells. Conversely, no apoptosis, necrosis or autophagy were detected after treatment, suggesting that reduced cell numbers in vitro are a result of diminished proliferation rather than cell death. Furthermore previous exposure to 10 ${\mu}g/ml$ DTCM-glutarimide sensitized both cell lines to ionizing radiation. Although more studies are needed to corroborate our findings, our results indicate that PDK1 may be useful as a therapeutic target to prevent progression and abnormal tissue dissemination of urothelial carcinomas.

• Asian Pacific Journal of Cancer Prevention
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• 제14권5호
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• pp.3191-3196
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• 2013

Leaf extracts of Cassia alata L (akapulko), traditionally used for treatment of a variety of diseases, were evaluated for their potential antitumor properties in vitro. MTT assays were used to examine the cytotoxic effects of crude extracts on five human cancer cell lines, namely MCF-7, derived from a breast carcinoma, SK-BR-3, another breast carcinoma, T24 a bladder carcinoma, Col 2, a colorectal carcinoma, and A549, a nonsmall cell lung adenocarcinoma. Hexane extracts showed remarkable cytotoxicity against MCF-7, T24, and Col 2 in a dose-dependent manner. This observation was confirmed by morphological investigation using light microscopy. Further bioassay-directed fractionation of the cytotoxic extract led to the isolation of a TLC-pure isolate labeled as f6l. Isolate f6l was further evaluated using MTT assay and morphological and biochemical investigations, which likewise showed selectivity to MCF-7, T24, and Col 2 cells with $IC_{50}$ values of 16, 17, and 17 ${\mu}g/ml$, respectively. Isolate f6l, however, showed no cytotoxicity towards the non-cancer Chinese hamster ovarian cell line (CHO-AA8). Cytochemical investigation using DAPI staining and biochemical investigation using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-a method used to detect DNA fragmentation-together with caspase assay, demonstrated apoptotic cell death. Spectral characterization of isolate f6l revealed that it contained polyunsaturated fatty acid esters. Considering the cytotoxicity profile and its mode of action, f6l might represent a new promising compound with potential for development as an anticancer drug with low or no toxicity to non-cancer cells used in this study.

• Asian Pacific Journal of Cancer Prevention
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• 제15권13호
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• pp.5259-5264
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• 2014

Background: CT based brachytherapy allows 3-dimensional (3D) assessment of organs at risk (OAR) doses with dose volume histograms (DVHs). The purpose of this study was to compare computed tomography (CT) based volumetric calculations and International Commission on Radiation Units and Measurements (ICRU) reference-point estimates of radiation doses to the bladder and rectum in patients with carcinoma of the cervix treated with high-dose-rate (HDR) intracavitary brachytherapy (ICBT). Materials and Methods: Between March 2011 and May 2012, 20 patients were treated with 55 fractions of brachytherapy using tandem and ovoids and underwent post-implant CT scans. The external beam radiotherapy (EBRT) dose was 48.6Gy in 27 fractions. HDR brachytherapy was delivered to a dose of 21 Gy in three fractions. The ICRU bladder and rectum point doses along with 4 additional rectal points were recorded. The maximum dose ($D_{Max}$) to rectum was the highest recorded dose at one of these five points. Using the HDRplus 2.6 brachyhtherapy treatment planning system, the bladder and rectum were retrospectively contoured on the 55 CT datasets. The DVHs for rectum and bladder were calculated and the minimum doses to the highest irradiated 2cc area of rectum and bladder were recorded ($D_{2cc}$) for all individual fractions. The mean $D_{2cc}$ of rectum was compared to the means of ICRU rectal point and rectal $D_{Max}$ using the Student's t-test. The mean $D_{2cc}$ of bladder was compared with the mean ICRU bladder point using the same statistical test. The total dose, combining EBRT and HDR brachytherapy, were biologically normalized to the conventional 2 Gy/fraction using the linear-quadratic model. (${\alpha}/{\beta}$ value of 10 Gy for target, 3 Gy for organs at risk). Results: The total prescribed dose was $77.5Gy{\alpha}/{\beta}10$. The mean dose to the rectum was $4.58{\pm}1.22Gy$ for $D_{2cc}$, $3.76{\pm}0.65Gy$ at $D_{ICRU}$ and $4.75{\pm}1.01Gy$ at $D_{Max}$. The mean rectal $D_{2cc}$ dose differed significantly from the mean dose calculated at the ICRU reference point (p<0.005); the mean difference was 0.82 Gy (0.48-1.19Gy). The mean EQD2 was $68.52{\pm}7.24Gy_{{\alpha}/{\beta}3}$ for $D_{2cc}$, $61.71{\pm}2.77Gy_{{\alpha}/{\beta}3}$ at $D_{ICRU}$ and $69.24{\pm}6.02Gy_{{\alpha}/{\beta}3}$ at $D_{Max}$. The mean ratio of $D_{2cc}$ rectum to $D_{ICRU}$ rectum was 1.25 and the mean ratio of $D_{2cc}$ rectum to $D_{Max}$ rectum was 0.98 for all individual fractions. The mean dose to the bladder was $6.00{\pm}1.90Gy$ for $D_{2cc}$ and $5.10{\pm}2.03Gy$ at $D_{ICRU}$. However, the mean $D_{2cc}$ dose did not differ significantly from the mean dose calculated at the ICRU reference point (p=0.307); the mean difference was 0.90 Gy (0.49-1.25Gy). The mean EQD2 was $81.85{\pm}13.03Gy_{{\alpha}/{\beta}3}$ for $D_{2cc}$ and $74.11{\pm}19.39Gy_{{\alpha}/{\beta}3}$ at $D_{ICRU}$. The mean ratio of $D_{2cc}$ bladder to $D_{ICRU}$ bladder was 1.24. In the majority of applications, the maximum dose point was not the ICRU point. On average, the rectum received 77% and bladder received 92% of the prescribed dose. Conclusions: OARs doses assessed by DVH criteria were higher than ICRU point doses. Our data suggest that the estimated dose to the ICRU bladder point may be a reasonable surrogate for the $D_{2cc}$ and rectal $D_{Max}$ for $D_{2cc}$. However, the dose to the ICRU rectal point does not appear to be a reasonable surrogate for the $D_{2cc}$.