• Title/Summary/Keyword: tumor development

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Combination of Poly-Gamma-Glutamate and Cyclophosphamide Enhanced Antitumor Efficacy Against Tumor Growth and Metastasis in a Murine Melanoma Model

  • Kim, Doo-Jin;Kim, Eun-Jin;Lee, Tae-Young;Won, Ji-Na;Sung, Moon-Hee;Poo, Haryoung
    • Journal of Microbiology and Biotechnology
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    • v.23 no.9
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    • pp.1339-1346
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    • 2013
  • Conventional chemotherapeutic regimens often accompany severe side effects and fail to induce complete regression of chemoresistant or relapsing metastatic cancers. The need for establishing more efficacious anticancer strategies led to the development of a combined modality treatment of chemotherapy in conjunction with immunotherapy or radiotherapy. It has been reported that poly-gamma-glutamate (${\gamma}$-PGA), a natural polymer composed of glutamic acids, increases antitumor activity by activating antigen-presenting cells and natural killer (NK) cells. Here, we investigated the antitumor effect of ${\gamma}$-PGA in combination with cyclophosphamide in a murine melanoma model. Whereas cyclophosphamide alone directly triggered apoptosis of tumor cells in vitro, ${\gamma}$-PGA did not show cytotoxicity in tumor cells. Instead, it activated macrophages, as reflected by the upregulation of surface activation markers and the secretion of proinflammatory factors, such as nitric oxide and tumor necrosis factor ${\alpha}$. When the antitumor effects were examined in a mouse model, combined treatment with cyclophosphamide and ${\gamma}$-PGA markedly suppressed tumor growth and metastasis. Notably, ${\gamma}$-PGA treatment dramatically increased the NK cell population in lung tissues, coinciding with decreased metastasis and increased survival. These data collectively suggest that ${\gamma}$-PGA can act as an immunotherapeutic agent that exhibits a synergistic antitumor effect in combination with conventional chemotherapy.

The origin-of-cell harboring cancer-driving mutations in human glioblastoma

  • Lee, Joo Ho;Lee, Jeong Ho
    • BMB Reports
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    • v.51 no.10
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    • pp.481-483
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    • 2018
  • Glioblastoma (GBM) is the most common and aggressive form of human adult brain malignancy. The identification of the cell of origin harboring cancer-driver mutations is the fundamental issue for understanding the nature of GBM and developing the effective therapeutic target. It has been a long-term hypothesis that neural stem cells in the subventricular zone (SVZ) might be the origin-of-cells in human glioblastoma since they are known to have life-long proliferative activity and acquire somatic mutations. However, the cell of origin for GBM remains controversial due to lack of direct evidence thereof in human GBM. Our recent study using various sequencing techniques in triple matched samples such as tumor-free SVZ, tumor, and normal tissues from human patients identified the clonal relationship of driver mutations between GBM and tumor-free SVZ harboring neural stem cells (NSCs). Tumor-free SVZ tissue away from the tumor contained low-level GBM driver mutations (as low as 1% allelic frequency) that were found in the dominant clones in its matching tumors. Moreover, via single-cell sequencing and microdissection, it was discovered that astrocyte-like NSCs accumulating driver mutations evolved into GBM with clonal expansion. Furthermore, mutagenesis of cancer-driving genes of NSCs in mice leads to migration of mutant cells from SVZ to distant brain and development of high-grade glioma through the aberrant growth of oligodendrocyte precursor lineage. Altogether, the present study provides the first direct evidence that NSCs in human SVZ is the cell of origin that develops the driver mutations of GBM.

Evaluation of the Pathogenesis of Tumor Development from Endometriosis by Estrogen Receptor, P53 and Bcl-2 Immunohistochemical Staining

  • Esmaili, Haidarali;Vahedi, Amir;Mohajeri, Shiva;Mostafidi, Elmira;Azimpouran, Mahzad;Behzad, Mohammad Naghavi
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.12
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    • pp.5247-5250
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    • 2016
  • Objective: Endometriosis, one of the most common estrogen dependent gynecological disorders, can present as both benign and malignant disease. The prevalence of tumoral transformation is 0.7-1.6% and the most common tumors are clear cell and endometrioid carcinomas. Unfortunately, the pathogenesis of transformation is unknown. For this purpose, we examined molecular alterations in ovarian endometriosis and endometriosis-associated tumors. Methods: Using the data bank of Alzahra hospital pathology department and paraffin blocks from appropriate cases were identified. Sections were cut and stained for 3 markers: estrogen receptor, P53 and bcl2. Correlations between findings were investigated. Results: Nineteen cases of endometriosis-associated tumor and 19 cases of endometriosis were identified. Staining for bcl2 was documented in 14 of 19 (73.7%) of endometriosis-associated tumor cases and also 7 of 19 (36.8%) endometriosis cases (P=0.02). Only 3 of the 19 (15.8%) endometriosis-associated tumors exhibited positive staining for estrogen receptors, compared with 14 of 19 (73.7%) endometriosis cases (P<0.001). Positive staining for P53 was noted in 5 of 19 (31.6%) endometriosis-associated ovarian tumor samples but was absent in endometriosis samples (0%), (P =0.008). Conclusions: Endometriosis-associated tumors appear to be associated with overexpression of bcl2 and P53 and reduced expression of Estrogen receptor. These finding may help to diagnose tumoral transformation with a background of endometriosis.

Liver Tumor Detection Using Texture PCA of CT Images (CT영상의 텍스처 주성분 분석을 이용한 간종양 검출)

  • Sur, Hyung-Soo;Chong, Min-Young;Lee, Chil-Woo
    • The KIPS Transactions:PartB
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    • v.13B no.6 s.109
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    • pp.601-606
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    • 2006
  • The image data amount that used in medical institution with great development of medical technology is increasing rapidly. Therefore, people need automation method that use image processing description than macrography of doctors for analysis many medical image. In this paper. we propose that acquire texture information to using GLCM about liver area of abdomen CT image, and automatically detects liver tumor using PCA from this data. Method by one feature as intensity of existent liver humor detection was most but we changed into 4 principal component accumulation images using GLCM's texture information 8 feature. Experiment result, 4 principal component accumulation image's variance percentage is 89.9%. It was seen this compare with liver tumor detecting that use only intensity about 92%. This means that can detect liver tumor even if reduce from dimension of image data to 4 dimensions that is the half in 8 dimensions.

VEGF Expression and Microvessel Density in Salivary Gland Tumor (타액선 종양에서 VEGF의 발현 및 미세혈관밀도의 의의)

  • Park Chul-Won;Kim Su-Young;Kim Kyung-Rae;Lee Hyung-Seok;Paik Seung-Sam;Park Yong-Wook;Tae Kyung
    • Korean Journal of Head & Neck Oncology
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    • v.21 no.2
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    • pp.183-189
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    • 2005
  • Objectives: Angiogenesis is the process of new blood vessel development from preexisting vessel. The growth of tumor is dependent on angiogenesis. This study was aimed to determine the role of the VEGF expression and MVD(microvessel density) in salivary gland tumors and to analyze the correlation between the expression of VEGF/MVD, and clinical manifestation. Material and Methods: We analyzed the expression of VEGF and average MVD and neo-MVD in the 57 cases of salivary gland tumors by immunohistochemistry. Results: VEGF expression was higher in malignant tumors than in benign tumors. Average and neo-MVD were not different in benign tumor and malignant tumor. There was a tendency of positive correlation between VEGF expression and MVD but it was not statistically significant. Stage, T stage and recurrance rate were not correlated with VEGF expression, average-MVD and neo-MVD. Expression of VEGF, average-MVD and neo-MVD were significantly increased in Warthin's tumor compared with pleomorphic adenoma. Conclusion: Overexpression of VEGF has an important role in malignant salivary gland tumors.

The Effect of Tumor Necrosis Factor (TNF) on Gene Expression of Surfactant Protein A, B, and C (Tumor Necrosis Factor가 Surfactant Protein A, B, C의 유전자 발현에 미치는 영향에 관한 실험적 연구)

  • Choi, Jin-Won;Sohn, Jang-Won;Yang, Seok-Chul;Yoon, Ho-Joo;Shin, Dong-Ho;Park, Sung-Soo
    • Tuberculosis and Respiratory Diseases
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    • v.48 no.4
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    • pp.513-521
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    • 2000
  • Background : TNF may play an important role(central mediator) in the development of an acute respiratory distress syndrome. Since TNF induced lung injury in the acute respiratory distress syndrome and abnormalities in surfactant function have been described in acute respiratory distress syndrome, the authors investigated the effects of TNF on the regulation of surfactant protein A, B and C mRNA accumulation. Methods : The effects of TNF on gene expression of surfactant protein A, B, and C were analyzed using filter hybridization, 12 and 24 hours after intravenous injection of TNF in rats. Results : 1. The accumulation of SP-A mRNA in the TNF treated group (12 and 24 hours after TNF injection) was significantly decreased by 22.9% and 27.4%, respectively, compared to the control group (P<.025, P<.025). 2. The accumulation of SP-B mRNA in 24 hours after TNF treated group was significantly decreased by 20.5% compared to that of the control group(P<.01). 3. The accumulation of SP-C mRNA in 12 hours after TNF treated group was significantly decreased by 31% the compared to that of the control group(P<.01). Conclusions : These findings indicate the marked inhibitory effects of tumor necrosis factor on surfactant proteins expression in vivo. This finding. in turn, supports the idea of inhibitory effects of tumor necrosis factor on surfactant proteins expression as it relates to pathogenesis of acute respiratory distress syndrome.

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New Tumor Metastasis Suppressor Gene from Korean Tiger Shark (Scyliorhinus torazame)

  • CHO Jung Jong;LEE Jae Hyung;LEE Sang-Jun;LIM Woon Ki;KIM Yung-Jin;KIM Kyu-Won;KIM Young Tae
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.30 no.6
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    • pp.984-991
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    • 1997
  • New tumor suppressor gene, snm23, homologous to human nm23/NDP kinase (human nucleoside diphosphate kinase) gene whose product has a tumor metastasis inhibitory activity, was first cloned from Korean tiger shark (Scyliorhinus forazame) skin cDNA library constructed by using a $\lambda$ ZAP-II cDNA synthesis kit. About $1\times10^5$ plaques were screened and several positive plaques were isolated and confirmed by second screening. The phagemid containing a positive clone from the Uni-Zap XR vector was excised in vivo and the gene containing the tumor metastasis suppressor protein was named as snm23. Cloned gene, snm23, was sequenced with ABI-PRISM 310 Genetic Analyzer. The nucleotide and deduced amino acid sequences of snm23 have shown an open reading frame consisting of 450 base pairs that correspond to a protein of 150 amino acid residues, with a calculated molecular mass of 16.8 kDa. Sequence comparison of snm23 with human nm23/NDP kinase was performed by using Blast protein data base of National Center for Biotechnology Information. In order to determine tissue specificity, reverse transcription-polymerase chain reaction (RT-PCR) was used. Good expression level of snm23/NDP kinase was detected at the tissues from skin, cartilage, and liver of Korean tiger shark.

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Anti-inflammatory and Anti-tumor Effects of Tetragonia tetragonoides Extracts (번행초 추출물의 항염증 및 종양억제 효과)

  • Choi, Hye Jung;Yee, Sung-Tae;Kwon, Gi-Seok;Joo, Woo Hong
    • Microbiology and Biotechnology Letters
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    • v.43 no.4
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    • pp.391-395
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    • 2015
  • We examined the anti-inflammatory effect and anti-tumor activity of Tetragonia tetragonioides crude extracts and fractions. The anti-inflammatory activity of T. tetragonioides was exuded through the inhibition of lipopolysaccharide (LPS, $1{\mu}g/ml$), induced nitric oxide (NO) and interleukin (IL)-$1{\beta}$ production. The production of IL-6 and tumor necrosis factor $(TNF)-{\alpha}$ also decreased in LPS induced RAW264.7 cells after treatment with polysaccharide (PS) fraction. Furthermore, the hexane (HX) fraction strongly inhibited the granulocytes macrophage-colony stimulating factor (GM-CSF) production. In ICR mice previously inoculated with Sarcoma 180, the life prolongation effects were 16.67% with an intraperitoneal injection of methanol (MeOH) extract and polysaccharide fraction at a dose of 100 mg/kg/day. The results are an important preliminary step toward the development of effective anti-inflammatory and anti-tumor agents using T. tetragonioides.

Gamma Knife Radiosurgery for Low Grade Glioma - Long-Term Follow-up Results - (양성 신경교종의 감마나이프 방사선수술 - 장기 추적 결과 -)

  • Chun, Sae Myoung;Lim, Young Jin;Leem, Won;Kim, Tae Sung;Kim, Gook Ki;Rhee, Bong Arm
    • Journal of Korean Neurosurgical Society
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    • v.30 no.sup2
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    • pp.273-280
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    • 2001
  • Objectives : The purpose of this study is to assess the long-term outcome and delayed complications of Gamma Knife radiosurgery for low grade glioma(LGG). Methods : Among 31 patients of LGG who had been treated by using Leksell Gamma Knife between March 1992 and December 1996, we could follow up more than 5 years(range 5-9 years) in 17 patients and evaluated their clinical feature, changes of tumor volume and post-radiosurgical complications. Results : During the mean follow-up period of 7.6 years, the tumor was decreased in 5 patients(29.4%), unchanged in 4(23.5%), increased in 4(23.5%) and recurred in 4(23.5%). The tumor control rate was 52.9%(9/17). We have experienced eighteen postradiosurgical complications in 10 patients(58.8%). Early complication was none and delayed complications included radiation necrosis with cyst in ten cases, bleeding in five, radiation-induced edema in one and malignant transformation in one. Two patients ultimately died as a result of tumor progression during the follow-up period. The mortality rate was 11.7%. Conclusion : Gamma Knife radiosurgery may be useful as an adjunctive therapy for small volume, deep-seated LGG. Although radiosurgery can effectively prevent growth of solid tumor, several delayed complications such as radiation necrosis, cyst formation, bleeding or malignant transformation can develop during the long-term followup period. Because of the possible slow growth rate of LGG and development of the delayed complications, the long-term efficacy of radiosurgery requires further analysis.

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3D-culture models as drug-testing platforms in canine lymphoma and their cross talk with lymph node-derived stromal cells

  • An, Ju-Hyun;Song, Woo-Jin;Li, Qiang;Bhang, Dong-Ha;Youn, Hwa-Young
    • Journal of Veterinary Science
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    • v.22 no.3
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    • pp.25.1-25.16
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    • 2021
  • Background: Malignant lymphoma is the most common hematopoietic malignancy in dogs, and relapse is frequently seen despite aggressive initial treatment. In order for the treatment of these recurrent lymphomas in dogs to be effective, it is important to choose a personalized and sensitive anticancer agent. To provide a reliable tool for drug development and for personalized cancer therapy, it is critical to maintain key characteristics of the original tumor. Objectives: In this study, we established a model of hybrid tumor/stromal spheroids and investigated the association between canine lymphoma cell line (GL-1) and canine lymph node (LN)-derived stromal cells (SCs). Methods: A hybrid spheroid model consisting of GL-1 cells and LN-derived SC was created using ultra low attachment plate. The relationship between SCs and tumor cells (TCs) was investigated using a coculture system. Results: TCs cocultured with SCs were found to have significantly upregulated multidrug resistance genes, such as P-qp, MRP1, and BCRP, compared with TC monocultures. Additionally, it was revealed that coculture with SCs reduced doxorubicin-induced apoptosis and G2/M cell cycle arrest of GL-1 cells. Conclusions: SCs upregulated multidrug resistance genes in TCs and influenced apoptosis and the cell cycle of TCs in the presence of anticancer drugs. This study revealed that understanding the interaction between the tumor microenvironment and TCs is essential in designing experimental approaches to personalized medicine and to predict the effect of drugs.