• Asian Pacific Journal of Cancer Prevention
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• 제15권7호
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• pp.2971-2977
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• 2014

Background: Long non-coding RNAs (lncRNAs) have been recently observed in various human cancers. However, the role of lncRNAs in pancreatic duct adenocarcinoma (PDAC) remains unclarified. The aim of this study was to detect the expression of lncRNA MALAT1 in PDAC formalin-fixed, paraffin embedded (FFPE) tissues and to investigate the clinical significance of the MALAT1 level. Methods: The expression of MALAT1 was examined in 45 PDAC and 25 adjacent non-cancerous FFPE tissues, as well as in five PDAC cell lines and a normal pancreatic epithelium cell line HPDE6c-7, using qRT-PCR. The relationship between MALAT1 level and clinicopathological parameters of PDAC was analyzed with the Kaplan-Meier method and Cox proportional hazards model. Results: The relative level of MALAT1 was significantly higher in PDAC compared to the adjacent normal pancreatic tissues (p=0.009). When comparing the MALAT1 level in the cultured cell lines, remarkably higher expression of MALAT1 was found in aspc-1 PDAC cells compared with the immortal pancreatic duct epithelial cell line HPDE6c-7 (q=7.573, p<0.05). Furthermore, MALAT1 expression level showed significant correlation with tumor size (r=0.35, p=0.018), tumor stage (r=0.439, p=0.003) and depth of invasion (r=0.334, p=0.025). Kaplan-Meier analysis revealed that patients with higher MALAT1 expression had a poorer disease free survival (p=0.043). Additionally, multivariate analysis indicated that overexpression of MALAT1, as well as the tumor location and nerve invasion, was an independent predictor of disease-specific survival of PDAC. Conclusion: MALAT1 might be considered as a potential prognostic indicator and may be a target for diagnosis and gene therapy for PDAC.

• Asian Pacific Journal of Cancer Prevention
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• 제15권2호
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• pp.831-835
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• 2014

Background: Predictor factors determining complete response to treatment are still not clearly defined. We aimed to evaluate clinicopathological features, risk factors, treatment responses, and survival analysis of patient with advanced nonseminomatous GCTs (NSGCTs). Materials and Methods: Between November 1999 and September 2011, 140 patients with stage II and III NSGCTs were referred to our institutions and 125 patients with complete clinical data were included in this retrospective study. Four cycles of BEP regimen were applied as a first-line treatment. Salvage chemotherapy and/or high-dose chemotherapy (HDCT) with autologous stem cell transplantation were given in patients who progressed after BEP chemotherapy. Post-chemotherapy surgery was performed in selected patients with incomplete radiographic response and normal tumor markers. Results: The median age was 28 years. For the good, intermediate and poor risk groups, compete response rates (CRR) were, 84.6%, 67.9% and 59.4%, respectively. Extragonadal tumors, stage 3 disease, intermediate and poor risk factors, rete testis invasion were associated with worse outcomes. There were 32 patients (25.6%) with non-CR who were treated with salvage treatment. Thirty-one patients died from GCTs and 94% of them had stage III disease. Conclusions: Even though response rates are high, some patients with GCTs still need salvage treatment and cure cannot be achieved. Non-complete response to platinium-based first-line treatment is a negative prognostic factor. Our study confirmed the need for a prognostic and predictive model and more effective salvage approaches.

• Journal of Korean Neurosurgical Society
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• 제48권1호
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• pp.20-30
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• 2010

Objective : We determined whether the expression of GRIM-19 is correlated with pathologic types and malignant grades in gliomas, and determined the function of GRIM-19 in human gliomas. Methods : Tumor tissues were isolated and frozen at $-80^{\circ}C$ just after surgery. The tissues consisted of normal brain tissue (4), astrocytomas (2), anaplastic astrocytomas (2), oligodendrogliomas (13), anaplastic oligodendrogliomas (11), and glioblastomas (16). To profile tumor-related genes, we applied RNA differential display using a $Genefishing^{TM}$ DEG kit, and validated the tumor-related genes by reverse transcription polymerase chain reaction (RT-PCR). A human glioblastoma cell line (U343MG-A) was used for the GRIM-19 functional studies. The morphologic and cytoskeletal changes were examined via light and confocal microscopy. The migratory and invasive abilities were investigated by the simple scratch technique and Matrigel assay. The antiproliferative activity was determined by thiazolyl blue Tetrazolium bromide (MTT) assay and FACS analysis. Results : Based on RT-PCR analysis, the expression of GRIM-19 was higher in astrocytic tumors than oligodendroglial tumors. The expression of GRIM-19 was higher in high-grade tumors than low-grade tumors or normal brain tissue; glioblastomas showed the highest expression. After transfection of GRIM-19 into U343MG-A, the morphology of the sense-transfection cells became larger and more spindly. The antisensetransfection cells became smaller and rounder compared with wild type U343MG-A. The MTT assay showed that the sense-transfection cells were more sensitive to the combination of interferon-$\beta$ and retinoic acid than U343MG-A cells or antisense-transfection cells; the antiproliferative activity was related to apoptosis. Conclusion : GRIM-19 may be one of the gene profiles which regulate cell death via apoptosis in human gliomas.

• 동의생리병리학회지
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• 제26권5호
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• pp.687-692
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• 2012

Schizandra chinensis extract has been known to possess a variety of efficacy including antitumor. However, it remains unclear how schizandrin, which is a major biological active ingredient of Schizandra chinensis, exerts antitumor effect. This study was designed to investigate the mechanism by which schizandrin inhibits tumor growth and metastasis. In in vivo test using tumor model mice injected with B16BL6 cell line, mice treated with 10 and 100 ${\mu}g/ml$ schizandrin showed a significant inhibition by $73.79{\pm}6.43%$ and $90.46{\pm}1.72%$, respectively, compared with positive tumor controls. Schizandrin did not exert a significant toxicity for the normal cells (HUVECs) and tumor cell lines (A549, B16BL6, Du145, Huh7). Treatment with schizandrin at 10 and 100 ${\mu}g$/head significantly inhibited the tumor-induced angiogenesis by $68.04{\pm}32.21%$ and $103.8{\pm}34.99%$ compared with the positive control group, respectively. Using in vivo lung metastasis model, tumor metastasis assay revealed that 10 and 100 ${\mu}g$/head schizandrin significantly decreased the metastatic lung tumor by $37.51{\pm}8.15%$ and $75.53{\pm}4.38%$ compared with positive controls, respectively. On the other hand, schizandrin did not affect the adherence of B16BL6 cell line to extracellular matrix protein. These results demonstrate that schizandrin exerts inhibitory effect on tumor growth and metastasis by inhibiting angiogenesis. This study thus suggest that schizandrin may be a candidate molecule target for cancer drug development.

• 한국임상수의학회지
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• 제27권3호
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• pp.232-239
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• 2010

개에서 자연발생한 유선종양으로부터 채취, 배양된 세포주 2개를 확립하고 특성을 분석하였다. 9세 령의 퍼그 종 개와 동일연령의 토이푸들 종의 개에 발생한 종양을 무균 상태를 유지하여 수술적으로 채취한 후 primary culture를 실시하였다. 두 종양의 조직병리검사에서는 각각 선암종과 혼합암종이 진단되었으며, 이후 두 마리 모두 전이로 인해 폐사하였다. 배양된 종양세포는 1년 이상의 기간 동안 60회 이상 계대를 반복하면서 형태학적으로 일관성을 유지하였고, 특성분석을 위해 광학현미경검사, 성장곡선 산출, 배가 시간 계산, 누드 마우스에 이종이식, 면역조직 화학검사를 실시하였다. 각 세포주는 다각형의 긴 세포형태를 보였으며, 세포질 연결을 형성하였으며, 배가 시간은 각각 47.1 시간과 18.6 시간이었다. 암컷 누드마우스의 등 부위에 피하이식 후 4주 이내에 10마리 중 9마리에서 촉진이 가능한 종괴의 형성이 확인되었으며, 면역조직화학검사 시 한 세포주에서는 keratin과 cytokeratin 8에서 다른 세포주에서는 smooth muscle actin과 cytokeratin 8에서 강한 염색성이 확인되었다. 두 세포주는 개의 유선종양의 시험관내, 체내 연구에 있어 모두 유용하게 사용될 수 있을 것으로 생각된다.

• KSBB Journal
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• 제13권4호
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• pp.357-363
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• 1998

The antitumor effects of mice fed with cell lysate of Lactobacillus plantarum were studied. The abdominal cancer induced by Sarcoma-180 was markedly inhibited and the expected life span was extended by 60% for the Balb/c mice fed with L. plantarum cell lysate for two weeks. A similar result was obtained for the rat inoculated with Spontaneous Osteosarcoma(SOS). The primary tumor volume of SOS was reduced by 70% for the rats fed with L. plantarum cell lysate (100mg/kg/day) for one week before the inoculation of SOS, while only 42% for the rats fed with the same amount of cell lysate for one week after the inoculation of tumor cell line, SOS. As lung was the metastasis site of SOS, the weight of lung was measured to determine the degree of metastasis inhibition by the L. plantarum cell lysate feeding. The rats fed with cell lysate for one week showed a remarkable inhibition of lung metastasis by 63%(before) and 46%(after), respectively. These results indicate that the feeding of L. plantarum cell lysate to mouse or rat can induce a strong stimulation of mucosal or systemic immune system and these effects results in an efficient antitumor activity.

• The Korean Journal of Physiology and Pharmacology
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• 제13권2호
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• pp.115-121
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• 2009

Functional defects in mitochondria are involved in the induction of cell death in cancer cells. We assessed the toxic effect of camptothecin against the human cervical and uterine tumor cell line SiHa with respect to the mitochondria-mediated cell death process, and examined the combined effect of camptothecin and anticancer drugs. Camptothecin caused apoptosis in SiHa cells by inducing mitochondrial membrane permeability changes that lead to the loss of mitochondrial membrane potential, decreased Bcl-2 levels, cytochrome c release, caspase-3 activation, formation of reactive oxygen species and depletion of GSH. Combination of camptothecin with other anticancer drugs (carboplatin, paclitaxel, doxorubicin and mitomycin c) or signaling inhibitors (farnesyltransferase inhibitor and ERK inhibitor) did not enhance the camptothecin-induced cell death and caspase-3 activation. These results suggest that camptothecin may cause cell death in SiHa cells by inducing changes in mitochondrial membrane permeability, which leads to cytochrome c release and activation of caspase-3. This effect is also associated with increased formation of reactive oxygen species and depletion of GSH. Combination with other anticancer drugs (or signaling inhibitors) does not appear to increase the anti-tumor effect of camptothecin against SiHa cells, but rather may reduce it. Combination of camptothecin with other anticancer drugs does not seem to provide a benefit in the treatment of cervical and uterine cancer compared with camptothecin monotherapy.

• 약학회지
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• 제59권4호
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• pp.164-169
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• 2015

In the present study, we determined the effect of $18{\beta}$-glycyrrhetinic acid ($18{\beta}$-GA) in the mice model bearing xenografts of HT-29 human colon cancer cell line. Data from the cytotoxicity assay displayed that $18{\beta}$-GA induced cell death in HT-29. The cytotoxicity was enhanced as the $18{\beta}$-GA treatment was prolonged. In case of 72 hrs treatment, $LD_{50}$ of $18{\beta}$-GA was approximately $90{\mu}M$, and the efficacy at $100{\mu}M$ of $18{\beta}$-GA appeared to be equivalent to that of doxorubicin at $1{\mu}M$. Based on the in vitro data, we tested the anti-tumor effect of $18{\beta}$-GA in thymic mice (Balb/c strain). Xenograft tumors were generated by subcutaneous injection of HT-29 ($3{\times}10^6cells/mouse$) to mice and the mice were treated intraperitoneally with $18{\beta}$-GA ($50{\mu}g/time/mouse$) every other day for 4 times. The tumor volumes were measured for a period of 14 days. Data displayed that the $18{\beta}$-GA treatment reduced the tumor volumes (P < 0.05) as compared to control mice. However, this activity was demolished when athymic mice (Balb/c nu/nu) were used instead of thymic mice. This observation appeared that T lymphocyte played an important role in the anti-tumor activity. In conclusion, our results indicate that $18{\beta}$-GA has anti-tumor activity in HT-29 tumor-bearing mice, which may be associated with T cells.

• International Journal of Oncology
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• 제55권4호
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• pp.960-972
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• 2019

MicroRNAs (miRNAs/miRs) are a class of small non-coding RNAs that play pivotal roles in cancer physiology as important epigenetic regulators of gene expression. Several miRNAs have been previously discovered that regulate the proliferation of the colorectal cancer (CRC) cell line HCT116. In the present study, one of these miRNAs, miR-5191, was characterized as a tumor suppressor in CRC cells. Transfection with miR-5191 led to a significant decrease in cell proliferation, invasiveness, tumor sphere-forming ability and tumor organoid growth, as determined via trypan blue, Transwell, sphere culture and organoid culture assays, respectively. Flow cytometric analyses revealed that miR-5191 induced the cell cycle arrest and apoptosis of CRC cells. Additionally, the expression of miR-5191 was downregulated in CRC tumor tissues compared with in normal tissues, as measured by reverse transcription-quantitative PCR analysis. Ribosomal protein S6 kinase β1 (RPS6KB1) was identified as a direct target of miR-5191. Ectopic expression of RPS6KB1 suppressed the function of miR-5191. Intratumoral injection of miR-5191 mimic suppressed tumor growth in HCT116 xenografts. These findings suggested a novel tumor-suppressive function for miR-5191 in CRC, and its potential applicability for the development of anticancer miRNA therapeutics.

• Molecules and Cells
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• 제40권5호
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• pp.346-354
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• 2017

Long interspersed nuclear element-1 (LINE-1) is a retrotransposon that contains a CpG island in its 5'-untranslated region. The CpG island of LINE-1 is often heavily methylated in normal somatic cells, which is associated with poor prognosis in various cancers. DNA methylation can differ between formalin-fixed paraffin-embedded (FFPE) and frozen tissues. Therefore, this study aimed to compare the LINE-1 methylation status between the two tissue-storage conditions in gastric cancer (GC) clinical samples and to evaluate whether LINE-1 can be used as an independent prognostic marker for each tissue-storage type. We analyzed four CpG sites of LINE-1 and examined the methylation levels at these sites in 25 FFPE and 41 frozen GC tissues by quantitative bisulfite pyrosequencing. The LINE-1 methylation status was significantly different between the FFPE and frozen GC tissues (p < 0.001). We further analyzed the clinicopathological features in the two groups separately. In the frozen GC tissues, LINE-1 was significantly hypomethylated in GC tissues compared to their corresponding normal gastric mucosa tissues (p < 0.001), and its methylation status was associated with gender, differentiation state, and lymphatic and venous invasion of GC. In the FFPE GC tissues, the methylation levels of LINE-1 differed according to tumor location and venous invasion of GC. In conclusion, LINE-1 can be used as a useful methylation marker for venous invasion in both FFPE and frozen tumor tissues of GC.