• Title/Summary/Keyword: metastatic cells

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Long Non-coding RNAs are Differentially Expressed in Hepatocellular Carcinoma Cell Lines with Differing Metastatic Potential

  • Fang, Ting-Ting;Sun, Xiao-Jing;Chen, Jie;Zhao, Yan;Sun, Rui-Xia;Ren, Ning;Liu, Bin-Bin
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.23
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    • pp.10513-10524
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    • 2015
  • Background: Metastasis is a major reason for poor prognosis in patients with cancer, including hepatocellular carcinoma (HCC). A salient feature is the ability of cancer cells to colonize different organs. Long non-coding RNAs (lncRNAs) play important roles in numerous cellular processes, including metastasis. Materials and Methods: In this study, the lncRNA expression profiles of two HCC cell lines, one with high potential for metastasis to the lung (HCCLM3) and the other to lymph nodes (HCCLYM-H2) were assessed using the Arraystar Human LncRNA Array v2.0, which contains 33,045 lncRNAs and 30,215 mRNAs. Coding-non-coding gene co-expression (CNC) networks were constructed and gene set enrichment analysis (GSEA) was performed to identify lncRNAs with potential functions in organ-specific metastasis. Levels of two representative lncRNAs and one representative mRNA, RP5-1014O16.1, lincRNA-TSPAN8 and TSPAN8, were further detected in HCC cell lines with differing metastasis potential by qRT-PCR. Results: Using microarray data, we identified 1,482 lncRNAs and 1,629 mRNAs that were differentially expressed (${\geq}1.5$ fold-change) between the two HCC cell lines. The most upregulated lncRNAs in H2 were RP11-672F9.1, RP5-1014O16.1, and RP11-501G6.1, while the most downregulated ones were lincRNA-TSPAN8, lincRNA-CALCA, C14orf132, NCRNA00173, and CR613944. The most upregulated mRNAs in H2 were C15orf48, PSG2, and PSG8, while the most downregulated ones were CALCB, CD81, CD24, TSPAN8, and SOST. Among them, lincRNA-TSPAN8 and TSPAN8 were found highly expressed in high lung metastatic potential HCC cells, while lowly expressed in no or low lung metastatic potential HCC cells. RP5-1014O16.1 was highly expressed in high lymphatic metastatic potential HCC cell lines, while lowly expressed in no lymphatic metastatic potential HCC cell lines. Conclusions: We provide the first detailed description of lncRNA expression profiles related to organ-specific metastasis in HCC. We demonstrated that a large number of lncRNAs may play important roles in driving HCC cells to metastasize to different sites; these lncRNAs may provide novel molecular biomarkers and offer a new basis for combating metastasis in HCC cases.

Fine Needle Aspiration Cytology of Hepatocellular Carcinoma - A Study on 247 Cases - (간세포암종의 세침흡인 세포학적 소견 - 247예에 대한 연구 -)

  • Lee, Kwang-Gil;Lee, Jong-Tae;Choi, Soo-Im;Park, Chan-Il
    • The Korean Journal of Cytopathology
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    • v.1 no.1
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    • pp.1-17
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    • 1990
  • Hepatocellular carcinoma (HCC) is malignant tumor frequently occurring in Koreans. There have been few reports regarding the cytologic findings of fine needle aspiration (FNA) of HCC. Most have suggested a diagnostic problem in the cytology distinguishing HCC from some benign hepatic lesions-for example, a regeneration nodule in cirrhosis and liver cell adenoma. In spite of its high frequency in Korea, no cytologic study has been reported, concerning the FNA of HCC. In an attempt to achieve cytologic criteria for the diagnosis of HCC, the authors studied retrospectively cytopathologic findings of 247 cases of HCC. These cases were confirmed either by histoiogic examination including lobectomy, biopsy, or ceil block material, or, when tissue diagnosis was unavailable, by a high serum alpha-fetoprotein level (over 400 I. U.). All aspiration smears were stained by the Papanicolaou method. In each case, the smears were analyzed for cell patterns and various cytomorphology of the tumor cells. The smear background was assessed for the presence of tumor cell necrosis and inflammatory components and compared to that of metastatic carcinomas. The cell patterns were classified as trabecular, acinar, dispersed, and irregular. The cytologic parameters analyzed included the degree of nuclear atypia and the presence of mitoses, intranuclear cytoplasmic inclusions, nucleolar prominency, endothelial lining, multinucleated giant cells, eosinophiic globules, bile, and Mallory body. Most of the FNA of HCC showed markedly cellular smears. The tumor cells were most frequently arranged in a trabecular pattern (80.3%). The irregular (12.6%), the acinar (5.5%), and the dispersed patterns (1.7%) followed in decreasing frequency. Individual hepatoma cells were larger than normal liver cells. However, they had morphologic features characteristic of the hepatic cells the cells were round or polygonal, their cytoplasm was abundant and granular with eosinophilic or amphophilic stainability, and their nuclei were round to oval, located centrally, and tended to have prominent nucleoli. Anaplasia and pleomorphism of tumor cells were generally mild to moderate. These findings existed even in very well differentiated cases. Mitotic figures were present in about 85% of the cases. Prominent nucleoli were observed only in about half the cases. The frequency of other cytologic features was as follows intranuclear cytoplasmic inclusion in 86.8% : endothelial lining in 56.1% : bile in 19.8% : and giant cells in 60.1%. Clear cells were often present in 11.7%, Most aspiration smears of HCC displayed clean background without necrosis or inflammatory material in contrast to the dirty, necrotic background of metastatic cancers and cholangiocarcinomas. Based on the above mentioned features, it is suqqested that the cytologic critieria most important for the diagnosis of HCC include a markedly cellular smear, trabecular pattern, hepatocytoid appearance of tumor cells, endothelial lining, the presence of bile, giant cells, intranuclear cytoplasmic inclusions, and prominent nucleoli, Among these, trabecular pattern, endothelial lining, giant cells and clean smear background are points to be considered in differentiating HCC from metastatic and cholangiocellular carcinoma.

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Cytologic Features and Distribution of Primary Sites of Malignant Cells in Cerebrospinal Fluid - Analysis of 1,438 Specimeus - (뇌척수액내 종양세포의 원발부위 분석 및 세포학적 특징 - 총 1,438예 분석 -)

  • Kim, Yeon-Mee;Jeon, Mi-Yeong;Chi, Je-Geun
    • The Korean Journal of Cytopathology
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    • v.11 no.2
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    • pp.65-73
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    • 2000
  • Cytologlc evaluation of cerebrospinal fluid(CSF) is an effective mean for diagnosing many disorders involving the central nervous systems(CNS). One of the most important reasons for cytologic examination of CSF is to detect metastatic or primary neoplasms of the CNS. We did a retrospective study of 1,438 CSF specimens obtained between 1992 and 1996. A total of 1,205 adult and 233 pediatric CSF specimens from 947 patients were accessed at the Department of Pathology of Seoul National University Hospital and Children's Hospital, respectively. Among 1,438 CSF cytology specimens, 169 cases(11.8%, 77 patients) including 135 adult cases(59 patients) and 34 pediatric cases(18 patients) were positive for malignant cells. Diagnoses included 50 metastatic carcinomas(adult, 60; pediatric, 0); 46 malignant lymphomas(adult, 44; pediatric, 2); 21 leukemias(adult, 20; pediatric, 1); 4 retinoblastomas(adult, 0; pediatric 4); 2 rhabdomyosarcomas(adult, 0; pediatric, 2); 1 multiple myeloma(adult, 1; pediatric, 0), and 35 primary CNS neoplasms(adult, 10; pediatric, 25). The most commonly identified metastatic carcinomas in adults were adenocarcinoma. Their primary sites were the lung, gastrointestinal tract, and breast in order of frequency. The most common primary CNS neoplasm in children was medulloblastoma.

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Effect of Tea Polyphenols on the Adhesion of Highly Metastatic Human Lung Carcinoma Cell Lines to Endothelial Cells in Vitro

  • Zheng, Feng-Jin;Shi, Lin;Yang, Jun;Deng, Xiao-Hui;Wu, Yu-Quan;Yan, Xi-Qing;Huang, Ning
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.8
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    • pp.3751-3755
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    • 2012
  • Aim: Tea polyphenols are known to play roles in critical steps of human lung carcinoma cell metastasis. For understanding the mechanisms whereby they inhibit tumor metastasis, the present study was conducted to investigate their effects on the adhesion of highly metastatic lung carcinoma cell lines (PG cells) to endothelial cells (EC cells) and adhesion molecule expression in vitro. Methods: The expression of CD44 or CD54 in the PG cells was detected by flow cytometry and adhesion of PG cells to EC cells was assessed by confocal microscopy double fluorescence staining. Results: The results showed that tea polyphenols: (1) inhibited the expression of CD44 and CD54, two important adhesion molecules in the PG cells in a dose-dependent manner; (2) significantly blocked the adhesion of PG cells to EC cells not only in a state of rest but also when active; and (3) influenced CD44 and CD54 expression during the adhesion process of PG cells to EC cells. Conclusions: The data indicated that the blocking role of tea polyphenols in the adhesion of PG cells to EC cells is related to CD44 and CD54. The mechanism of tea polyphenol prevention of human lung carcinoma metastasis might be through inhibiting adhesion molecule expression to block cancer cell adhesion.

Anti-metastatic and Anti-angiogenic Activities of Ekong-san and Its Metabolites by Human Intestinal Bacteria (이공산의 혈관신생 및 암전이 억제효과에 관한 연구)

  • Kang Chang Hee;Myung Eu Gene;Kang Hee;Choi Sun Mi;Shim Bum Sang;Kim Sung Hoon;Choi Seung Hoon;Shin Hyeun Kyoo;Kim Dong Hyun;Ahn Kyoo Seok
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.18 no.6
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    • pp.1686-1693
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    • 2004
  • Ekong-san(EKS) was expected to have inhibitory effects on angiogenesis, considering the fact that its constituents such as Ginseng Radix, Glycyrrhizae Radix and Citri Pericarpium were reported to inhibit angiogenesis. Moreover, recently several metabolites transformed by the human intestinal microflora were reported to enhance effectiveness compared to their crude drugs. Based on these data, this study was designed to confirm whether the EKS metabolites (EKS-M) can significantly exert the anti-angiogenic and anti-metastatic activites. Hence, with EKS and EKS-M, viability assay, proliferation assay, in vitro tube formation assay, gelatin zymogram assay, in vitro invasion assay were carried out. EKS showed less toxicity in ECV304 and HT1080 cells than EKS-M. EKS-M inhibited the proliferation of HT1080 cells by 30% at 200㎍/㎖ and 42% at 400 ㎍/㎖ respectively. Also, EKS-M degraded the tube network at 200㎍/㎖. EKS and EKS-M inhibited the expression of MMP-9 at 200 and 400㎍/㎖ in HT1080 cells. EKS reduced the invasive activity of HT1080 cells through matrigel coated transfilter atthe concentration of 200㎍/㎖ more effectively than EKS-M. These data suggest that EKS and EKS-M has anti-angiogenic and anti-metastatic activities.

Fine Needle Aspipration Cytology of Metastatic Pulmonary Seminoma - A Cese Report - (세침흡인 세포검사로 진단된 폐에 전이한 정상피종 - 1예 보고 -)

  • Jeong, Hwa-Sook;Lee, Geon-Kook;Kim, Wun-Jae;Earm, Jae-Ho;Song, Hyung-Geun
    • The Korean Journal of Cytopathology
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    • v.7 no.1
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    • pp.97-102
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    • 1996
  • Fine needle aspiration cytology of a pulmonary mass was performed on a 51-year-old man who had a left testicular mass. Cytologic features were composed of a homogeneous population of malignant cells associated with a background of foamy and lacelike material. The cellular features were characterized by monomorphous cell proliferation of relatively regular large cells, generally isolated or grouped. Occasionally, fine blanching stroma with large tumor cells and scanty lymphocytes were noted. The tumor cells had a round, regular nucleus, prominent round nucleoli, and a thin rim of cytoplasm containing large vacuoles or lacunae filled with glycogen. The fine needle aspiration cytologic diagnosis was highly consistent with metastatic seminoma from testis and less likely primary or other metastatic carcinoma. The diagnosis of resected testicular mass was classic seminoma. Despite the fact that cytopathologists were not familial with diagnosis of seminoma due to clinician's lack of interest in fine needle aspiration cytology of germ cell tumors including seminoma, it appears that a diagnosis of this tumor should not be problematic in cytologic material if specific histologic criteria are applied.

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Ultrasonographic Diagnosis of Metastatic Intracavitary Cardiac Aortic Body Tumor in a Dog (개에서 전이성 심장내 대동맥체 종양의 초음파적 진단)

  • 박인철
    • Journal of Veterinary Clinics
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    • v.17 no.1
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    • pp.173-177
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    • 2000
  • A 3-year-old male Tosa was presented the severe dyspnea, emaciation and dehy dration. By echocardiograpy, right ventricle was found to be a mobile mass dynamically occluding the right ostium atrioventriculare in the systolic phase. At necropsy, 14 days after ultrasonography multiple tumor masses of various size were observed in the heart base, right ventricular lumen, myocardium, lung and liver. Histopathologically, the tumor cells, arranged in sheets or nests, were diagnosed as metastatic intracavitary cardiac aortic body tumor

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STUDY ON mRNA EXPRESSION OF P21 AND P73 IN THE CELL LINES OF PRIMARY AND METASTATIC SQUAMOUS CELL CARCINOMA (원발성 및 전이성 구강편평세포암종 세포주에서 p21 및 p73 mRNA발현에 관한 연구)

  • Kang, Jeong-Hoon;Kim, Kyung-Wook;Lee, Jae-Hoon
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.27 no.6
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    • pp.483-490
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    • 2001
  • There were many controversies in the cause and progress of tumorigenesis. Recently, studies on the mutation of genes related to the tumor have extensively been performed due to development of molecular biology. Structural and morphological changes of chromosomes, which are related to the abnormal activation of oncogenes or inactivation of tumor suppression genes, transform the normal cells into the tumor cells. p53 and Rb are well known tumor suppressor genes, while oncogenes include c-myc, bcl-2 and ras, etc. When exposed to cell damaging agents, p53 inhibits cell growth by inducing transcription of p21. Especially p73, which is homo-logy of p53, frequently deleted in melanoma, neuroblastoma, colon cancer, and breast cancer, when over produced, p73 activates the transcription of p21, bax-1 and inhibits cell growth by inducing apoptosis. For study on mRNA expression of p21 and p73, normal oral keratinocytes, and cell lines of primary and metastatic oral squamous cell carcinoma were cultured and then electrophoresis and RT-PCR(reverse transcription-polymerase chain reaction) were performed. 1. The mRNA of p21 and p73 in normal oral keratinocyte expressed lower than that of primary squamous cell carcinoma. 2. The mRNA of p21 in metastatic oral squamous carcinoma cell lines was expressed as various patterns compared with that of normal oral keratinocyte. 3. In the metastatic oral squamous cell lines, the mRNA of HN8 expressed higher than that of HN12 or HN19. 4. The mRNA of p73 in primary oral squamous cell lines expressed 4-5 times higher than that of normal keratinocyte. 5. In metastatic oral squamous cell lines, there was no significant expression of p73 mRNA compared with that of normal oral keratinocyte. From the results obtained in this study, mRNA expression of p73 in primary oral squamous cell lines was remarkable, while mRNA expression of p21 and p73 in metastatic oral squamous cell lines were statistically insignificant.

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Adoptive Cell Therapy of Melanoma with Cytokine-induced Killer Cells

  • Kim, Ji Sung;Kim, Yong Guk;Pyo, Minji;Lee, Hong Kyung;Hong, Jin Tae;Kim, Youngsoo;Han, Sang-Bae
    • IMMUNE NETWORK
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    • v.15 no.2
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    • pp.58-65
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    • 2015
  • Melanoma is the most aggressive skin cancer and its incidence is gradually increasing worldwide. Patients with metastatic melanoma have a very poor prognosis (estimated 5-year survival rate of <16%). In the last few years, several drugs have been approved for malignant melanoma, such as tyrosine kinase inhibitors and immune checkpoint blockades. Although new therapeutic agents have improved progression-free and overall survival, their use is limited by drug resistance and drug-related toxicity. At the same time, adoptive cell therapy of metastatic melanoma with tumor-infiltrating lymphocytes has shown promising results in preclinical and clinical studies. In this review, we summarize the currently available drugs for treatment of malignant melanoma. In addition, we suggest cytokine-induced killer (CIK) cells as another candidate approach for adoptive cell therapy of melanoma. Our preclinical study and several previous studies have shown that CIK cells have potent anti-tumor activity against melanomas in vitro and in an in vivo human tumor xenograft model without any toxicity.