• Asian Pacific Journal of Cancer Prevention
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• 제13권11호
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• pp.5729-5733
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• 2012

Background and Objectives: This study aimed to present the clinicopathological characteristics and treatment of patients with bladder carcinoma with sarcomatoid differentiation at our institution. Methods: Between 1995-2009, 950 patients were followed-up for bladder carcinoma. Among them, 14 patients with sarcomatoid carcinoma were retrospectively reviewed, and their clinical, pathological features and treatment were recorded. Results: Median age of the patients was 65 years (range: 41-86 years), 12 (86%) being male and 2 (14%) female. All the patients presented with hematuria and 11 (88%) had a history of smoking. The tumor growth pattern was solid in 10 patients, papillary in 2, and mixed in 2. In all, 5 of the patients had urothelial carcinoma with sarcomatoid differentiation and 9 were diagnosed with sarcomatoid carcinoma. Five patients underwent radical cystectomy with ileal conduit surgery, 2 patients refused cystectomy, and 8 patients underwent re-TUR. Following diagnosis, 12 of the patients died in mean 10.7 months (range: 1-48 months). Conclusion: Urothelial carcinomas with sarcomatoid features are aggressive and are usually at advanced stage at the time of diagnosis. The outcomes of multimodal treatment are not satisfactory. Significant findings of the present study are that early diagnosis positively affect survival and that gemcitabine and cisplatin in combination can positively affect survival.

• Asian Pacific Journal of Cancer Prevention
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• 제13권2호
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• pp.689-692
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• 2012

Objective: To investigate correlations between adenosine triphosphate chemotherapy response assay (ATP-CRA) and clinical outcomes after ATP-CRA-based chemotherapy for drug selection in patients receiving intravesical chemotherapy to prevent recurrence of superficial bladder cancer after surgery. Methods: The chemosensitivities of 12 anticancer drugs were evaluated, including 5-Fu ADM, and EPI, using ATP-CRA and primary tumor cell culture in 54 patients. In addition, a further 58 patients were treated according to clinical experience. Differences in post-chemotherapeutical effects between drug sensitivity assay and experience groups were compared. Results: The evaluable rate of the test was 96.3%, the clinical effective rate was 80.8%, the sensitivity rate was 97.6% (41/42), the specificity was 20%, the total predicting accuracy was 74.3%, the positive predictive value was 83.7% (41/49), the negative predictive value was 66.7% (2/3); in the drug sensitivity test group, the clinical effective rate was 80.8%, the experience group response rate was 63.8%, with a significant difference in clinical effects between the ATP-based sensitivity and experience groups (${\chi}^2$=7.0153, P<0.01). Conclusion: ATP-CRA is a stable, accurate and potentially practical chemosensitivity test providing a predictor of chemotherapeutic response in patients with superficial bladder cancer.

• 대한한의학방제학회지
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• 제25권2호
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• pp.145-154
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• 2017

Objectives : Bufalin is one of the bioactive component of 'Sum Su (蟾酥)', which is obtained from the skin and parotid venom gland of toad. Bufalin has been known to possess the inhibitory effects on cell proliferation and inducing apoptosis in various cancer cells. The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) has concerned, because it can selectively induce apoptotic cell death in many types of malignant cells, while it is relatively non-toxic to normal cells. Here, we investigated whether bufalin can trigger TRAIL-induced apoptotic cell death in EJ human bladder cancer cells. Methods : Effects on the cell viability and apoptotic activity were quantified using MTT assay and flow cytometry analysis, respectively. To investigate the morphological change of nucleus, DAPI staining was performed. Protein expressions were measured by immunoblotting. Results : A combined treatment with bufalin (10 nM) and TRAIL (50 ng/ml) significantly promoted TRAIL-mediated growth inhibition and apoptosis in EJ cells. The apoptotic effects were associated with the up-regulation of death receptor proteins, and the down-regulation of cFLIP and XIAP. Moreover, our data showed that bufalin and TRAIL combination activated caspases and subsequently increased degradation of poly(ADP-ribose) polymerase. Conclusions : Taken altogether, the nontoxic doses of bufalin sensitized TRAIL-mediated apoptosis in EJ cells. Therefore, bufalin might be an effective therapeutic strategy for the safe treatment of TRAIL-resistant bladder cancers.

• Asian Pacific Journal of Cancer Prevention
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• 제14권6호
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• pp.3773-3778
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• 2013

Increased oxidative stress and changes in DNA methylation are frequently detected in bladder cancer patients. We previously demonstrated a relationship between increased oxidative stress and hypomethylation of the transposable long-interspersed nuclear element-1 (LINE-1). Promoter hypermethylation of a tumor suppressor gene, runt-related transcription factor 3 (RUNX3), may also be associated with bladder cancer genesis. In this study, we investigated changes of DNA methylation in LINE-1 and RUNX3 promoter in a bladder cancer cell (UM-UC-3) under oxidative stress conditions, stimulated by challenge with $H_2O_2$ for 72 h. Cells were pretreated with an antioxidant, tocopheryl acetate for 1 h to attenuate oxidative stress. Methylation levels of LINE-1 and RUNX3 promoter were measured by combined bisulfite restriction analysis PCR and methylation-specific PCR, respectively. Levels of LINE-1 methylation were significantly decreased in $H_2O_2$-treated cells, and reestablished after pretreated with tocopheryl acetate. Methylation of RUNX3 promoter was significantly increased in cells exposed to $H_2O_2$. In tocopheryl acetate pretreated cells, it was markedly decreased. In conclusion, hypomethylation of LINE-1 and hypermethylation of RUNX3 promoter in bladder cancer cell line was experimentally induced by reactive oxygen species (ROS). The present findings support the hypothesis that oxidative stress promotes urothelial cell carcinogenesis through modulation of DNA methylation. Our data also imply that mechanistic pathways of ROS-induced alteration of DNA methylation in a repetitive DNA element and a gene promoter might differ.

• Asian Pacific Journal of Cancer Prevention
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• 제13권6호
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• pp.2799-2806
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• 2012

The aim of this study was to elucidate the role of the integrin-linked kinase (ILK) gene in development of human bladder transitional cell carcinoma (BTCC). Expression of ILK protein and ILK mRNA in 56 cases of human BTCC tissue and in 30 cases of adjacent normal bladder tissue was detected by immunohistochemistry S-P and reverse transcription polymerase chain reaction (RT-PCR), respectively. Four specific miRNA RNAi vectors targeting human ILK were synthesized and transfected into BIU-87 cells by liposome to obtain stable expression cell strains. The influence of ILK on proliferation of BTCC was detected by MTT, FCM on athymic mouse tumorigenesis. The positive rate of ILK protein in BTCC tissue (53.6%) was much higher than adjacent normal bladder tissue (10.0%) (p<0.05). Similarly, expression of ILK mRNA in BTCC tissue ($0.540{\pm}0.083$) was significantly higher than in adjacent normal bladder tissue ($0.492{\pm}0.070$) (p<0.05). MTT showed that the proliferation ability of miRNA-ILK transfected group was clearly decreased (p<0.05), the cell cycle being arrested in G0/G1-S, an tumorigenesis in vivo was also significantly reduced (p<0.05). ILK gene transcription and protein expression may be involved in the development of BTCC, so that ILK might be the new marker for early diagnosis and the new target for gene treatment.

• Asian Pacific Journal of Cancer Prevention
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• 제13권10호
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• pp.5053-5056
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• 2012

Background: Bladder cancer is one the most common malignancies of the genitourinary tract. The present study aimed to assess the epidemiology, of bladder cancer in Mazandaran, a large province in northern Iran as high-incidence cancer area, during a 2-year period. Methods: The data for this study were obtained from the population-based cancer registry of the Vice-Chancellory for Health Affairs of Mazandaran University of Medical Sciences and Mazandaran hospitals between March 1, 2010 and March 1, 2011. Demographic data, including sex, age, residency and symptoms were investigated through careful review of medical records. Using a questionnaire protocol, several variables were assessed for these cases such as smoking, history of opium, vegetable consumption habits, and history of other cancers. Results: A total of 112 cases were analyzed, 98 (87.5%) in men and 14 (12.5%) in women (mean age of $68.0{\pm}14.6$ years). Urban and rural residence were 60.7% and 39.3%. Tobacco and opium use were found in 45.5% and 21.4% of patients, respectively. Approximately 60% consumed vegetables an average of fewer than one time per day. Hematuria was the first symptom in these cases which were mainly diagnosed as having bladder cancer by ultrasonography. Conclusion: The results showed that bladder cancer tends to be found in the elderly and the male to female ratio is high. Macroscopic hematuria is a very important symptom for indicating probably urothelial tumor that should be followed up patients with transabdominal ultrasonography as a routine modality.

• 대한방사선치료학회지
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• 제16권2호
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• pp.9-17
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• 2004

목적 : 최근 CT, MRI 등 영상진단기술 및 방사선치료계획 소프트웨어 등이 획기적으로 발전하였음에도 불구하고 자궁경부암의 강내조사는 아직까지 A 점 등 ICRU 38에 근거한 치료계획을 보편적으로 사용하고 있다. CT를 이용한 3차원 강내조사 계획은 종양 및 정상조직에 대한 선량뿐 아니라 선량-용적 히스토그람(DVH)에 대한 정보를 제공한다. 본 연구에서는 CT를 이용하여 CTV에 목표선량을 조사하는 치료계획(CTV계획)과 ICRU 38에 근거한 치료계획(ICRU계획)을 시행하여 이 두 치료계획간에 종양선량, 직장선량, 방광선량 등을 비교하고 각각에 대한 DVH를 분석하였다. 대상 및 방법 : Ir-192 고선량율강내치료(HDR)를 시행 받은 11명의 환자를 대상으로 하였다. 강내조사계획은 외부방사선치료를 약 40Gy 시행한 후 수립되었으며 모든 환자에서 CT 모의치료기를 이용한 CT가 시행되었고 치료계획은 PLATO(Nucletron) v.14.2를 이용하였다. CT 영상에 CTV, 직장, 방광 등을 도시한 후 CTV에 $100\%$의 선량을 조사하는 치료계획 및 ICRU 38에 근거하여 A점에 $100\%$를 조사하는 치료계획을 수립하였다. 결과 : 11명 환자의 CTV 용적(평균${\pm}$표준편차)은 $21.8{\pm}26.6cm^3$, 직장 용적은 $60.9{\pm}25.0cm^3$, 방광용적은 $116.1{\pm}40.1cm^3$이었다. ICRU계획에서 $100\%$의 선량이 포함하는 용적은 $126.7{\pm}18.9cm^3$, CTV 계획에서는 $98.2{\pm}74.5cm^3$으로서 잔류종양의 크기가 4cm 이상인 1례에서는 ICRU계획 시 CTV 용적 $22.0cm^3$가 $100\%$ 등선량곡선에 포함되지 않는 것으로 나타났다. 잔류종양의 크기가 4cm 미만인 나머지 8례에서는 종양용적 $12.9{\pm}5.9cm^3$이 불필요하게 $100\%$ 이상의 선량이 조사되었다. ICRU 38의 권고에 따른 방광선량은 ICRU계획 및 CTV계획에서 각각 $90.1{\pm}21.3\%,\;68.7{\pm}26.6\%$이었고, 직장선량은 $86.4{\pm}18.3\%,\;76.9{\pm}15.6\%$이었다. 방광 및 직장선량 최대값도 ICRU계획에서 각각 $137.2{\pm}50.1\%,\;101.1{\pm}41.8\%$, CTV계획에서 $107.6{\pm}47.9\%,\;86.9{\pm}30.8\%$로서 CTV계획에서 정상조직에 조사되는 선량이 더 적게 나타났다. 그러나 잔류종양이 4cm 이상인 환자에서는 CTV계획에서 정상조직 선량이 견딤선량보다 현저히 높게 나타났다. DVH에서는 목표선량의 $80\%$ 이상을 받는 직장용적(V80rec)은 ICRU계획 및 CTV계획에서 각각 $1.8{\pm}2.4cm^3,\;0.7{\pm}1.0cm^3$, 방광용적 (V80bla)은 $12.2{\pm}8.9cm^3,\;3.5{\pm}4.1cm^3$로서 역시 CTV계획에서 정상조직이 적게 조사되었다. 결과 : 기존의 ICRU계획은 그 효과 및 안전성이 입증되었음에도 불구하고 CT를 이용한 CTV계획 등을 적용 한다면 잔류종양이 적은 경우 정상조직에 대한 조사를 줄이면서 잔류종양에 목표선량을 조사할 수 있을 것이다. 다만 잔류종양이 큰 경우는 정상조직에 대한 조사선량을 줄이기 위한 효과적 치료계획에 대한 연구가 필요할 것으로 판단된다.

• Radiation Oncology Journal
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• 제15권1호
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• pp.57-64
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• 1997

목적 : 자궁경부암환자의 근치목적의 방사선치료 성적을 보고하기에 앞서 본원에서 사용하고 있는 자궁강내치료기기의 선량투여 방법의 정확성을 평가해보고 각 장기의 흡수선량을 대변할수 있는 예측력이 어느정도인지 알아보고자 연구를 시행하였다. 대상 및 방법 : 조준필름의 측면사진에서는 본원에서 현재 사용중인 방광(SBD)과 직장(SRD)의 기준흡수점의 흡수선량을 확인 하였다. 골반강 자기공명상의 측면사진에서 종양의 두 횡축과 종축의 직경을 곱하여 종양부피(TV)를 측정하였고, 기본으로 사음되고 있는 등선량곡선을 그린후 선량기준점 A 의 등선량 곡선내에 자궁경부 종양이 포함되는지 대상 환자별로 확인하였으며, 방광(MBD)과 직장(MRD)에서 보여주는 최대흡수선량점의 값을 측정하였고, 또한 선량기준점 A의 등선량 곡선내에 포함되는 방광(HBV)과 직장(HRV)의 면적을 계산해 보았다. 결 과 : 45례를 대상으로 분석하였다. 이중 53%(24/45) 에서만이 선량기준점 A의 등선량곡선내에 종양이 잘 포함되었다. 적절한 포함정도는 병기보다는 원발종양의 크기와 통계학적으로 유의한 관련성을 보여주었으며 종양의 측면지름의 크기가 3cm 이상인 종양은 불충분한 포함을 보여 주었다. 조준필름의 측면상의 방광과 직장의 기준흡수선량값은 자기공명사진상의 방광과 직장의 최대흡수값과 각각 유의한 관계를 보여주지 못했으나, 조준필름의 직장의 흡수선량값(SRD)은 HRV 와 유의한 관련성을 보여주었다. HBV 이나 HRV 은 오히려 자기공명사진상에서 측정한 종양의 크기(TV) 와 유의한 연관성을 보여 주었다. 결론 : 본원에서 사용하고 있는 선량계산 방법은 개별적인 종양의 크기를 고려해주지 못하였으며, 특히 방광의 흡수선량계산에 있어서 실제 흡수선량을 대변할수 있는 예측도가 낮아서 이에 대한 환자 개개인의 종양의 특성을 고려한 선량계산이 필요하리라 사료되는 바이다.

• Environmental Analysis Health and Toxicology
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• 제14권1_2호
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• pp.13-19
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• 1999

Cisplatin is an inorganic complex formed by a central atom of platinum surrounded by chlorine and ammonia atoms in the cis position in the horizontal plane, Cisplatin is one of the most effective anticancer drug, widely used against various tumor such as testicular tumor, brain tumor, ovary tumor, bladder carcinoma, colon cancer etc. However its clinical use has been limited by nephrotoxicity, ototoxicity , gastrointestinal disturbances, myeloscrppression and allergic reactions. In these toxicities, dose related and cumulative nephrotoxicity is the major dose limit factor. So, to evaluate the protective effect of aspalactone on cisplatin nephrotoxicity in rats, both compounds were given intraperitoneally, Protective effects of aspalactone against nephrotoxicity of cisplatin were observed when aspalactone was administered to rats 1hr beforecisplatin injection. Hepatotoxicity induced by combination treatment of cisplatin and aspalactone was not observed. The present results indicate that aspalactone may provide protection against cisplatin nephrotoxicity, when it is given 1hr before cisplatin injection.

• BMB Reports
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• 제56권1호
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• pp.24-31
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• 2023

Urological cancers such as kidney, bladder, prostate, and testicular cancers are the most common types of cancers worldwide with high mortality and morbidity. To date, traditional cell lines and animal models have been broadly used to study pre-clinical applications and underlying molecular mechanisms of urological cancers. However, they cannot reflect biological phenotypes of real tissues and clinical diversities of urological cancers in vitro system. In vitro models cannot be utilized to reflect the tumor microenvironment or heterogeneity. Cancer organoids in three-dimensional culture have emerged as a promising platform for simulating tumor microenvironment and revealing heterogeneity. In this review, we summarize recent advances in prostate and kidney cancer organoids regarding culture conditions, advantages, and applications of these cancer organoids.