• Title/Summary/Keyword: Neoplastic cell transformation

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ACRYLAMIDE-INDUCED NEOPLASTIC TRANSFORMATION OF HUMAN EPITHELIAL CELLS IN CULTURE (Acrylamide가 인체상피세포의 발암화에 미치는 영향)

  • Kim, Sang-Kyu;Kim, Jin-Wook;Kim, Chin-Soo
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.34 no.6
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    • pp.602-610
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    • 2008
  • Purpose Acrylamide is present in significant quantities in a wide range of commonly consumed human foods. Carcinogenic risk of acrylamide through the consumption of food is a great public concern and in controversy, but it is not properly addressed due to the lack of evidence in humans. While a plenty of data is available on the carcinogenicity in animal models, the studies in humans are limited. Thus, the present study attempted to examine the carcinogenic potentials of acrylamide on the human epithelial cell, which is the target cell origin of the most cancers. Material and method & Result 1. Acrylamide was not cytotoxic up to $100{\mu}M$ as measured by MTT and LDH assays, indicating a relatively low toxicity of this substance in human epithelial cells. 2. The parameters of neoplastic cellular transformation such as cell saturation density, soft-agar colony formation and cell aggregation were analyzed to examine the carcinogenic potential of acrylamide. 3. The neoplastic transformation was further increased with the co-treatment of TPA 4. Antioxidants blocked the generation of Reactive Oxygen Species(ROS) and the GSH depleting agent dramatically increased the ROS production. 5. mRNA levels of fibronectin following acrylamide exposure was increased in a dose-dependent manner, indicating a possible biomarker of acrylamide-induced cellular transformation. Conclusion The present study will provide a valuable basis to compare the interspecies differences in response to carcinogenic potentials of acrylamide. The data on the interspecies differences are essential element in human risk assessment. Thus, our results obtained from the human epithelial cells will contribute to improving the risk assessment of human neoplasm including oral cancer.

DNAJB9 Inhibits p53-Dependent Oncogene-Induced Senescence and Induces Cell Transformation

  • Lee, Hyeon Ju;Jung, Yu-Jin;Lee, Seungkoo;Kim, Jong-Il;Han, Jeong A.
    • Molecules and Cells
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    • v.43 no.4
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    • pp.397-407
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    • 2020
  • DNAJB9 is known to be a member of the molecular chaperone gene family, whose cellular function has not yet been fully characterized. Here, we investigated the cellular function of DNAJB9 under strong mitogenic signals. We found that DNAJB9 inhibits p53-dependent oncogene-induced senescence (OIS) and induces neoplastic transformation under oncogenic RAS activation in mouse primary fibroblasts. In addition, we observed that DNAJB9 interacts physically with p53 under oncogenic RAS activation and that the p53-interacting region of DNAJB9 is critical for the inhibition of p53-dependent OIS and induction of neoplastic transformation by DNAJB9. These results suggest that DNAJB9 induces cell transformation under strong mitogenic signals, which is attributable to the inhibition of p53-dependent OIS by physical interactions with p53. This study might contribute to our understanding of the cellular function of DNAJB9 and the molecular basis of cell transformation.

EFFECTS OF HYDROQUINONE ON NEOPLASTIC TRANSFORMATION OF HUMAN EPITHELIAL CELLS IN CULTURE (Hydroquinone이 인체 상피세포의 발암화에 미치는 영향)

  • Sohn, Jung-Hee;Kim, Chin-Soo
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.32 no.3
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    • pp.218-228
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    • 2010
  • Components of dental resin-based restorative materials are reported to leach from the filling materials even after polymerization. Hydroquinone (HQ) is one of the major monomers used in the dental resin and is known as a carcinogen. Thus, carcinogenic risk of HQ leaching from the dental resin becomes a public health concern. The present study attempted to examine the carcinogenic potentials of HQ on the human epithelial cell, which is the target cell origin of the most of oral cancers. Cytotoxicity of HQ was observed above 50${\mu}M$ as measured by LDH assay, indicating a relatively low toxicity of this substance in human epithelial cells. The parameters of neoplastic cellular transformation such as cell saturation density, soft agar colony formation and cell aggregation were analyzed to examine the carcinogenic potential of HQ. The study showed that 2-week exposure of HQ showed the tendency of increase in the saturation density and the significant enhancement of soft agar colony formation at the highest dose, 50 ${\mu}M$ only. It is suggested that HQ has a weak potential of carcinogenicity. When cells were treated with HQ and TPA, a well-known tumor promoter, the parameters of neoplastic cellular transformation was significantly increased. This result indicates that the potential risk of carcinogenicity from HQ is largely dependent upon the presence of promoter. Exposure of 50 ${\mu}M$ HQ increased the time-dependent apoptosis as measured by the ELISA kit. This concentration coincides with a dose of neoplastic transformation, indicating a possible link between apoptosis and HQ-induced cellular transformation. Hydroquinone generated Reactive Oxygen Species (ROS) which was evidenced by the treatment of antioxidants such as trolox and N-acetyl cysteine and the GSH depleting agent, BSO. Antioxidants blocked the generation of ROS and the GSH depleting agent, BSO dramatically increased the ROS production. Since HQ is known to increase ROS production thru activation of transcriptional factor such as c-Myb and Pim-1, it is speculated that ROS generation by HQ plays a role in the activation of oncogene, which may lead to neoplastic transformation. In addition, ROS is involved in the alteration of signal transduction, which regulates the apoptosis in many cellular systems. Thus, ROS-mediated apoptosis may be involved in the HQ-induced carcinogenic processes. Protein kinase C (PKC) is known to play pivotal roles in neoplastic transformation of cells and its high expression is often found in a variety of types of tumors including oral cancer. PKC translocation of PKC-${\alpha}$ was observed following HQ exposure. Altered signaling system may also play a role in the transformation process. Taken together, HQ leached from the dental resin does not pose a significant threat as a cancer causing agent, but its carcinogenic potential can be significantly elevated in the presence of promoter. The mechanism of HQ-induced carcinogenesis involved ROS generation, apoptosis and altered signaling pathway. The present study will provide a valuable data to estimate the potential risk of HQ as a carcinogen and understand mechanism of HQ-induced carcinogenesis in human epithelial cells.

HIGH DOSE EXPOSURES OF VINYL ACETATE INDUCE NEOPLASTIC TRANSFORMATION OF HUMAN EPITHELIAL CELLS IN CULTURE (인체상피세포를 이용한 Vinyl acetate의 발암성 및 작용기전)

  • Cho, Jun-Hyun;Kim, Chin-Soo
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.33 no.5
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    • pp.437-444
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    • 2007
  • Vinyl acetate has been widely used for the manufacture of polyvinyl alcohol emulsion, which is primary ingredient of adhesive, paints, textile, paperboard coatings, etc. Since these products are plentiful and frequently used around us, workers and consumers are at health risk. International Agency for Research on Cancer(IARC) classified vinyl acetate as group 2B(possibly carcinogenic to humans). Among the organs targeted, the oral cavity is the most vulnerable organ affected by the carcinogenic effects of vinyl acetate. Since the origin of most of oral cancer is derived from the epithelial cells, it is important to understand the carcinogenic potential of vinyl acetate in human epithelial cells. Thus, the present study has attempted to utilize the immortalized human epithelial cell model to assess the carcinogenic potency of this chemical and to understand the underlying mechanisms.

Anaplastic Transformation of Follicular Thyroid Cancer in the Lung, Liver, Bone, and Adrenal Gland

  • Lee, Wonae;Kim, Dohee
    • International journal of thyroidology
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    • v.10 no.2
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    • pp.127-132
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    • 2017
  • Anaplastic transformation of differentiated thyroid cancer at distant metastatic sites is extremely rare and has a poor prognosis. It usually occurs in the thyroid gland or cervical lymph nodes. Here we report a case of anaplastic transformation arising at multiple distant metastatic sites including the lung, liver, adrenal gland, bone, and lymph nodes in a patient 3 years after total thyroidectomy for follicular thyroid cancer.

Rutin Suppresses Neoplastic Cell Transformation by Inhibiting ERK and JNK Signaling Pathways (Rutin의 ERK 및 JNK 신호전달체계 억제를 통한 암예방 효능)

  • Kang, Nam Joo
    • The Korean Journal of Food And Nutrition
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    • v.28 no.4
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    • pp.579-585
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    • 2015
  • Rutin is a well-known flavonoid found in buckwheat. Recent studies have demonstrated that the biological actions of rutin include anti-inflammatory and anti-cancer effects, but the underlying molecular mechanisms of these actions are not yet fully understood. Neoplastic cell transformation is considered a major event that contributes to carcinogenesis, and the present study aimed to determine whether rutin would exert anti-tumor effects via the results suggest that rutin exerted a potent inhibitory influence on the molecular activity of the MEK/ERK and MKK4/JNK pathways and strongly attenuated EGF-induced neoplastic cell transformation. These findings provide insight into the biological actions of rutin and the molecular basis for the development of new chemoprotective agents.

Segmentation by Contour Following Method with Directional Angle

  • Na, Cheol-Hun;Kim, Su-Yeong;Kang, Seong-Jun
    • Proceedings of the Korean Institute of Information and Commucation Sciences Conference
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    • 2012.10a
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    • pp.874-877
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    • 2012
  • This paper proposes the new method based on contour following method with directional angle to segment the cell into the nuclei. The object image was the Thyroid Gland cell image that was diagnosed as normal and abnormal(two types of abnormal : follicular neoplastic cell, and papillary neoplastic cell), respectively. The nuclei were successfully diagnosed as normal and abnormal. this paper, improved method of digital image analysis required in basic medical science for diagnosis of cells was proposed. The object image was the Thyroid Gland cell image with difference of chromatin patterns. To segment the cell nucleus from background, the region segmentation algorithm by edge tracing was proposed. And feature parameter was obtained from discrete Fourier transformation of image. After construct a feature sample group of each cells, experiment of discrimination was executed with any verification cells. As a result of experiment using features proposed in this paper, get a better segmentation rate(70-90%) than previously reported papers, and this method give shape to get objectivity and fixed quantity in diagnosis of cells. The methods described in this paper be used immediately for discrimination of neoplastic cells.

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Differential Expression of Cytokeratin 13 in Non-Neoplastic, Dysplastic and Neoplastic Oral Mucosa in a High Risk Pakistani Population

  • Farrukh, Sanniya;Syed, Serajuddaula;Pervez, Shahid
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.13
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    • pp.5489-5492
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    • 2015
  • Background: Gradual loss of cytokeratin 13 (CK13) may be linked with the severity of dysplastic changes and transformation to malignancy. In this study we assessed the differential expression of CK13 in normal, hyperplastic, dysplastic and cancerous oral mucosa. Materials and Methods: A total of 93 oral biopsies were collected during the 2011-2014 period. The biopsies were characterized as normal (19), hyperplastic (21), severely dysplastic/carcinoma in situ (16) and invasive oral squamous cell carcinoma (OSCC) (37) after morphological assessment. Formalin fixed paraffin embedded sections were stained with a monoclonal antibody against CK13 using the Envision technique. Immunohistochemically stained slides were then analyzed for CK13 expression. Results: CK13 was consistently and diffusely expressed in all normal and hyperplastic tissue biopsies from oral mucosa. Severely dysplastic/carcinoma in situ biopsies showed complete loss in 50% of cases, while in the remaining 50% expression was very focal and weak. OSCC cases showed complete or near complete loss of CK13 in all cases. Few cases showed weak expression in keratin pearls only. Conclusions: This study validates the utility of CK13 IHC as a useful immunohistochemical marker in routine diagnostic practice to make distinction between non-neoplastic from dysplastic and neoplastic (malignant) oral lesions.

Image Analysis for Discrimination of Neoplastic Cellis in Spatial Frequency Domain (종양세포식별을 위한 공간주파수영역에서의 화상해석)

  • 나철훈;김창원;김현재
    • The Journal of Korean Institute of Communications and Information Sciences
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    • v.18 no.3
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    • pp.385-396
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    • 1993
  • In this paper, a improved method of digital image analysis required in basic medical science for diagnosis of cells was proposed. The object image was the thyroid gland cell image, and the purpose was automatic discrimination of three classes cells(normal cell, follicular neoplastic cells, and papillary neoplastic cells) by difference of chromatin patterns. To segment the cell nucleus from background, the region segmentation algorithm by edge tracing was proposed. And feature parameter was obtained from discrete Fourier transformation of image. After construct a feature sample group of each cells, experiment of discrimination was executed with any verification cells. As a consequency of using features proposed in this paper, get a better recognition rate(70-90%) than previously reported papers, and this method give shape to get objectivity and fixed quantity in diagnosis of cells, The methods described in this paper be used immediately for discrimination of neoplastic cells.

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Chemical Transformation of Human Keratinocytes by 2,3,7,8-Tetrachlorodibenxo-$\rho$-dioxin

  • Kang, Mi-Kyung;Choi, Young-Sill;Ryeom, Tai-Kyung;Eom, Mi-Ok;Park, Mi-Sun;Jee, Seung-Won;Kim, Kang-Ryune;Kim, Ok-Hee;Kang, Ho-Il
    • Environmental Mutagens and Carcinogens
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    • v.26 no.3
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    • pp.69-76
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    • 2006
  • 2,3,7,8-Tetrachlorodibenzo-$\rho$-dioxin(TCDD) is a ubiquitous, persistent environmental contaminant and the most powerful carcinogen categorized by IARC. Although the mechanism of carcinogenesis by TCDD is poorly understood, several studies have shown that the skin is one of target organs far TCDD. In this study, we investigated the neoplastic transformation of human keratinocyte-derived cell line, HaCaT, by chemical transformation method using N-methyl-N'-nitro-N-nitrorsoguanidine(MNNG) and TCDD. We found that subsequent exposure to TCDD for 3 weeks after initial exposure to MNNG markedly induced transformed cells. It was suggested that TCDD can act as a potent promoter in HaCaT cells. Furthermore, these transformed cells showed morphological alternations in soft agar and increased telomerase activity. Therefore, the TCDD treatment of HaCaT cells by initiated with MNNG could promote neoplastic transformation without stimulation by exogenous growth factors. As a result, TCDD had a strong potency as a promoter in nontumorigenic immortalized human epidermal keratinocytes.

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