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

• Advances in Traditional Medicine
• /
• 제5권4호
• /
• pp.322-330
• /
• 2005

The plant Bryonia laciniosa (Family: Cucurbitaceae) has been indicated for the treatment of various diseases one among which is cancer. The purpose of this study was investigating experimentally the possible anti-tumor effect and antioxidant role of Bryonia laciniosa leaves in animal model. The methanol extract of Bryonia laciniosa (MEBL) administered at the doses of 62.5, 125 and 250 mg/kg in mice for 14 days after 24 h of tumor inoculation. The effect of MEBL on the growth of transplantable murine tumor, life span of EAC bearing mice, hematological profile and liver biochemical parameters (lipid peroxidation, antioxidant enzymes) were estimated. Treatment with MEBL decreased the tumor volume and viable cell count thereby increasing the life span of EAC bearing mice and brought back the hematological parameter more or less normal level. The effect of MEBL also decreases the levels of lipid peroxidation and increased the levels of glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT). The present work indicates that the methanol extract of Bryonia laciniosa exhibited significant antitumor and antioxidant activity in vivo.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권4호
• /
• pp.1675-1679
• /
• 2014

Objectives: MicroRNAs (miRNAs) are important regulators of many physiological and pathological processes, including tumorigenesis and metastasis. In this study, we sought to determine the underlying molecular mechanisms of metastatic cervical carcinoma by performing miRNA profiling. Methods: Tissue samples were collected from ten cervical squamous cancer patients who underwent hysterectomy and pelvic lymph node (PLN) dissection in our hospital, including four PLN-positive (metastatic) cases and six PLN-negative (non-metastatic) cases. A miRNA microarray platform with 1223 probes was used to determine the miRNA expression profiles of these two tissue types and case groups. MiRNAs having at least 4-fold differential expression between PLN-positive and PLN-negative cervical cancer tissues were bioinformatically analyzed for target gene prediction. MiRNAs with tumor-associated target genes were validated by quantitative reverse transcription-polymerase chain reaction (RT-PCR). Results: Thirty-nine miRNAs were differentially expressed (>4-fold) between the PLN-positive and PLN-negative groups, of which, 22 were up-regulated and 17 were down-regulated. Sixty-nine percent of the miRNAs (27/39) had tumor-associated target genes, and the expression levels of six of those (miR-126, miR-96, miR-144, miR-657, miR-490-5p, and miR-323-3p) were confirmed by quantitative (q)RT-PCR. Conclusions: Six MiRNAs with predicted tumor-associated target genes encoding proteins that are known to be involved in cell adhesion, cytoskeletal remodeling, cell proliferation, cell migration, and apoptosis were identified. These findings suggest that a panel of miRNAs may regulate multiple and various steps of the metastasis cascade by targeting metastasis-associated genes. Since these six miRNAs are predicted to target tumor-associated genes, it is likely that they contribute to the metastatic potential of cervical cancer and may aid in prognosis or molecular therapy.

• Asian Pacific Journal of Cancer Prevention
• /
• 제17권4호
• /
• pp.1785-1787
• /
• 2016

Granular cell tumor (GCT) of the oral cavity is a benign lesion. Half of oral GCTs demonstrate pseudocarcinomatous hyperplasia (PCH) of the mucosa which can mimic invasive islands of oral squamous cell carcinoma (SCC). Such similarity can be confusing when diagnosing or evaluating the two conditions, potentially leading to misdiagnosis or misclassification. Indeed, several misdiagnosed cases of oral GCT have been reported in the literature as OSCC or malignant oral GCT that resulted in unnecessary aggressive treatment for the affected patients. The aim of this study was to investigate if the cytokeratin pattern of the PCH can help in differentiating GCT from oral SCC. To distinguish between these two entities, we examined 12 patient specimens of oral GCT-PCH and oral SCC histologically and via immunohistochemistry (IHC) for CK13, CK17 and P75. The results suggest that the cytokeratin profile of PCH is similar to that of oral SCC. Therefore, consideration of IHC findings for epithelial markers alone may lead to erroneous diagnosis; thus, the presence of the granular tumor underneath the PCH and its immunopositivity for P75 or other neural definition markers can be essential to identify the underlying tumor and exclude oral SCC. Finally we recommend more studies on the molecular biology of PCH to understand how it can mimic oral SCC histologically without harboring its malignant phenotype clinically, which could have significant translational potential for understanding invasive oral SCC.

• 한국응용약물학회:학술대회논문집
• /
• 한국응용약물학회 1993년도 제2회 신약개발 연구발표회 초록집
• /
• pp.74-74
• /
• 1993

The in vitro cytotoxicity of SKI 2053R was evaluated against human tumor cell lines along with those of cisplatin and carboplatin using MTT assay. The cell lines tested were two human lung cancer cell lines and five human stomach cancer celt lines. The level of cytotoxic effects of SKI 2053R against two human lung cancer cell lines was located between cisplatin and carboplatin. However, the cytotoxic activity of SKI 2053R against five human stomach cancer cell lines was similar to that of cisplatin. SKI 2053R is considered to be selectively cytotoxic toward human stomach cancer cell lines. We carried out pharmacokinetic and ex vivo phrmacodynamic studies of SKI 2053R in beagle dogs to predict the clinical antitumor effect of SKI2053R, comparing with those of cisplatin and carboplatin. In ex vivo pharmacodynamics which used MTT assay as bioassay on the 2 lung and 5 stomach cancer cell, mean antitumor indexes (ATIs) of SKI 2053R were highest among three compounds in both lung and stomach cancer cell lines, especially in stomach cancer cell. Much higher ATI profile and maximal inhibition rates of SKI 2053R appeared in the stomach cancer cells will give desirable advantages to clinical trial s against gastric carcinoma. The anti tumor activity and target organ toxicity of SKI 2053R were compared with those of cisplatin on stomach cancer cell line, KATO III xenografted into nude BALB/c(nu/nu) mice. All groups of cisplatin and SKI 2053R showed active tumor regression. The inhibition rates(IR) of SKI 2053R were higher than that of cisplatin on the basis of mean IR. Though the loss of body weight was observed in all groups from the first week, the SKI 2053R group recovered it soon from the third week after the initiation of treatment, maintaining the most active anti tumor activity among three groups.

• 대한의생명과학회지
• /
• 제19권2호
• /
• pp.164-167
• /
• 2013

Osteoclasts are originated from hemopoietic progenitors of the monocyte/macrophage lineage and resorb mineralized tissues. Elevated osteoclast numbers and activity result in bone disease such as osteoporosis, Paget's disease, and tumor osteolysis. In order to identify the genes that are involved in osteoclast differentiation, microarray was performed after treated with RANKL for 12 h and 24 h in osteoclast precursors. The genes that changed by RANKL treatment were grouped by biological process or molecular function. Among them, the number of genes involved in signal transduction and nucleic acid binding was 6065 and 3066, respectively. When analyzed the number of genes changed more than 1.5 fold in the cells treated with RANKL for 12 h or 24 h compared to when RANKL was not treated, 83 and 62 genes were up-regulated; 56 and 62 genes were downregulated, respectively. To verify the microarray results, real-time RT-PCR for Cxcl1 and Slfn1genes that have not been reported yet related to osteoclast differentiation, as well as Ccl2 gene associated with osteoclast differentiation were carried out. Both experiments showed a similar result of more than 1.5 fold induction of these genes by RANKL treatment. These results suggest the possibility that Cxcl1 and Slfn1 may associate with osteoclastogenesis and provide that microarray is a useful tool to analyze the profile of genes changed during osteoclast differentiation by RANKL. Moreover, this gene profile contributes to understand the regulatory mechanisms involved in osteoclast differentiation and the pathogenesis, thus developing therapeutics of bone diseases such as osteoporosis.

• Molecular & Cellular Toxicology
• /
• 제5권1호
• /
• pp.44-50
• /
• 2009

This study was conducted to evaluate the inflammation mechanisms of tumor necrosis factor-$\alpha$ (TNF-$\alpha$), interleukin-4 (IL-4), and IL-$1{\beta}$-induced stimulation of A549 human epithelial cells. In the present study, A549 cells were stimulated with TNF-$\alpha$, IL-4 and IL-$1{\beta}$ to induce expression of chemokines and adhesion molecules involved in eosinophil chemotaxis. The effects of TNF-$\alpha$, IL-4 and IL-$1{\beta}$ on gene expression profiles in A549 cells were evaluated by oligonucleotide microarray and Real time RT-PCR. The gene expression profiles for the A549 cells varied depending on the cytokines. Also, the results of the microarray and Real time RT-PCR revealed that inflammatory-related genes were up-regulated in cytokine stimulated A549 cells. Cytokines can affect inflammation in A549 cells. A microarray-based genomic survey is a high-throughput approach that enables evaluation of gene expression in cytokine stimulated cell lines.

• Asian Pacific Journal of Cancer Prevention
• /
• 제17권3호
• /
• pp.1571-1576
• /
• 2016

Alteration of the acetylation status of chromatin and other non-histone proteins by HDAC inhibitors has evolved as an excellent epigenetic strategy in treatment of cancers. The present study was sought to identify compounds with positive pharmacological profiles targeting HDAC1. Analogues of Vorinostat synthesized by Cai et al, 2015 formed the test compounds for the present pharmacological evaluation. Hydroxamte analogue 6H showed superior pharmacological profile in comparison to all the compounds in the analogue dataset owing to its better electrostatic interactions and hydrogen bonding patterns. In order to identify compounds with even better high affinity and pharmacological profile than 6H and Vorinostat, virtual screening was performed. A total of 83 compounds similar to Vorinostat and 154 compounds akin to analogue 6H were retrieved. SCHEMBL15675695 (PubCid: 15739209) and AKOS019005527 (PubCid: 80442147) similar to Vorinostat and 6H, were the best docked compounds among the virtually screened compounds. However, in spite of having good affinity, none of the virtually screened compounds had better affinity than that of 6H. In addition SCHEMBL15675695 was predicted to be a carcinogen while AKOS019005527 is Ames toxic. From, our extensive analysis involving binding affinity analysis, ADMET properties predictions and pharmacophoric mappings, we report Vorinostat hydroxamate analogue 6H to be a potential candidate for HDAC inhibition in treatment of cancers through an epigenetic strategy.

• Asian Pacific Journal of Cancer Prevention
• /
• 제13권9호
• /
• pp.4793-4799
• /
• 2012

Hypoxia is commonly featured during glioma growth and plays an important role in the processes underlying tumor progression to increasing malignancy. Here we compared the gene expression profiles of rat C6 malignant glioma cells under normoxic and hypoxic conditions by cDNA microarray analysis. Compared to normoxic culture conditions, 180 genes were up-regulated and 67 genes were down-regulated under hypoxia mimicked by $CoCl_2$ treatment. These differentially expressed genes were involved in mutiple biological functions including development and differentiation, immune and stress response, metabolic process, and cellular physiological response. It was found that hypoxia significantly regulated genes involved in regulation of glycolysis and cell differentiation, as well as intracellular signalling pathways related to Notch and focal adhesion, which are closely associated with tumor malignant growth. These results should facilitate investigation of the role of hypoxia in the glioma development and exploration of therapeutic targets for inhibition of glioma growth.

• 대한수의학회지
• /
• 제47권1호
• /
• pp.85-89
• /
• 2007

A case of multicentric high grade T cell lymphoma is reported in a 5-year-old male Maltese dog with generalized lymphadenopathy. The dog showed depression, anorexia, blindness, jaundice, arrhythmia, and hematuria for 8 months. Complete blood count and chemistry profile revealed anemia and increased alanine transferase, alkaline phosphatase, total bilirubin, and total cholesterol. Grossly, most of lymph nodes, spleen, and liver were enlarged and neoplastic masses were occupied in these tissues. Histologically, massive accumulation of small noncleaved neoplastic lymphocytes with high mitotic figures was observed in all lymph nodes and spleen. Infiltration of neoplastic lymphocytes was also noted in the lung, liver, kidney, eye, skin, muscle, and bone marrow of femur. Immunohistochemistry revealed that tumor cells were CD3-positive and but CD79a-negative, consistent with T-cell lineage. In our best knowledge, this is the first report of multicentric lymphoma clarified the origin of tumor cells in Korea.