• 제목/요약/키워드: Cancer progression

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HQSAR Study on Imidazo[1,2-b]pyridazine Derivatives as p38 MAP Kinase Antagonists

  • Bhujbal, Swapnil P.;Keretsu, Seketoulie;Cho, Seung Joo
    • Journal of Integrative Natural Science
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    • v.11 no.2
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    • pp.107-112
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    • 2018
  • p38 MAP kinase belongs to the Mitogen-activated protein (MAP) kinase family; a serine/threonine kinase. It plays an important role in intracellular signal transduction pathways. It is associated with the development and progression of various cancer types making it a crucial drug target. Present study involves the HQSAR analysis of recently reported imidazo[1,2-b]pyridazine derivatives as p38 MAP kinase antagonists. The model was generated with Atom (A), bond (B), chirality (Ch), and hydrogen (H) parameters and with different set of atom counts to improve the model. An acceptable HQSAR model ($q^2=0.522$, SDEP=0.479, NOC=5, $r^2=0.703$, SEE=0.378, BHL=97) was developed which exhibits good predictive ability. A contribution map for the most active compound (compound 17) illustrated that hydrogen and nitrogen atoms in the ring A and ring B, as well as nitrogen atom in ring C and the hydrogen atom in the ring D provided positive activity in inhibitory effect while, the least active compound (compound 05) possessed negative contribution to inhibitory effect. Hence, analysis of produced HQSAR model can provide insights in the designing potent and selective p38 MAP kinase antagonists.

The Relationship between the Expression of Melanoma Differentiation-Associated Gene-7/Interleukin-24 (MDA-7/IL-24) and Clinicopathological Features in Colorectal Adenocarcinomas

  • Seo, Boram;Hong, Young Seob;Youngmin, Youngmin;Roh, Mee Sook
    • Biomedical Science Letters
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    • v.18 no.4
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    • pp.413-419
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    • 2012
  • The melanoma differentiation-associated gene-7 (MDA-7) protein, also known as interleukin-24 (IL-24), is a novel candidate of tumor suppressor that can induce apoptosis experimentally in a variety of human malignant cells. However, there have been few studies about its role in colorectal cancer. We performed immunohistochemical detection of MDA-7/IL-24 in 399 tissue samples from primary colorectal adenocarcinoma patients using a tissue microarray. Western blotting was then done to confirm the immunohistochemical observations. MDA-7/IL-24 immunoreactivity was observed in 116 (29.1%) of the 399 colorectal adenocarcinoma cases. Analysis of the MDA-7/IL-24 expression by Western blotting confirmed the immunohistochemical results. The tumors with a negative MDA-7/IL-24 expression more frequently showed poor differentiation (P=0004), lymph node metastasis (P=0.001), deep invasion (P=0.008) and high stage (P=0.001). A subset of colorectal adenocarcinoma revealed a decreased expression of MDA-7/IL-24, and this was associated with progressive pathologic features. These findings suggest that loss of MDA-7/IL-24 expression may play a role in tumor growth and progression of colorectal adenocarcinomas.

Effect of Neem (Azadirachta indica) oil on the progressive growth of a spontaneous T cell lymphoma

  • Mallick, Sanjaya Kumar;Gupta, Vivekanand;Singh, Mahendra Pal;Vishvakarma, Naveen Kumar;Singh, Nisha;Singh, Sukh Mahendra
    • Advances in Traditional Medicine
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    • v.7 no.5
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    • pp.459-465
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    • 2008
  • The present study was undertaken to investigate the effect of in vivo administration of neem oil intra-peritoneally (i.p.) to mice bearing a progressively growing transplantable T cell lymphoma of spontaneous origin, designated as Daltons lymphoma (DL), on the tumor growth. Mice were administered various doses of neem oil mixed in groundnut oil, which was used as a diluting vehicle or for administration to control DL-bearing mice. Administration of neem oil resulted in an acceleration of tumor growth along with a reduction in the survival time of the tumor-bearing host. Neem oil administered DL-bearing mice showed an augmented apoptosis in splenocytes, bone marrow cells and thymocytes along with an inhibition in the anti-tumor functions of tumor-associated macrophages. Thus this study gives an altogether a novel information that neem oil instead of the popular belief of being anti-tumor and immunoaugmentary may in some tumor-bearing conditions, behave in an opposite way leading to an accelarated tumor progression along with a collapse of the host's anti-tumor machinery. These observations will thus have long lasting clinical significance, suggesting caution in use of neem oil for treatment of cancer.

Anaplastic Carcinoma of Thyroid Gland (갑상선 역형성암종)

  • 이원종;심윤상;오경균;이용식
    • Korean Journal of Bronchoesophagology
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    • v.1 no.1
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    • pp.151-158
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    • 1995
  • Anaplastic carcinoma of thyroid gland account for no more than 10% of thyroid cancer, but it shows extremely poor prognosis. The purpose of this study is to review the outcome of patients with anaplastic carcinoma over the span of 5 years and to determine the patterns of clinical presentation, age, sex and other possible prognostic variables. We analyzed 30 cases of anaplastic carcinoma retrospectively from 1991 to 1995. There were 14 men and 16 women. There age ranged 33 to 75 years with a mean of 61.0 years. Sixteen patients presented with transformationqr of well differentiated carcinoma to anaplastic carcinoma, 1 with rapid in-crease in the size of long standing goiter, 8 with rapidly growing neck mass and 4 with meta static disease. Twenty-eight patients(93.3%) showed cervical lymphnode metastasis at presentation and twenty three patients(76.6%) showed laryngotracheal invasion. Nine patients (30.3%) showed distant metastasis. Treatment modalities included surgical resection, external irradiation, radioactive iodine and systemic chemotherapy. At decision making of treatment plan, we considered completeness of initial surgery, uptake rate of whole body radioactive io-dine scan, locoregional progression and distant metastasis. The median survival was 6.8 months and three cases survived beyond 12 months.

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Myosin X and Cytoskeletal Reorganization

  • Ikebe, Mitsuo;Sato, Osamu;Sakai, Tsuyoshi
    • Applied Microscopy
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    • v.48 no.2
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    • pp.33-42
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    • 2018
  • Myosin X is one of myosin superfamily members having unique cellular functions on cytoskeletal reorganization. One of the most important cellular functions of myosin X is to facilitate the formation of membrane protrusions. Since membrane protrusions are important factors for diverse cellular motile processes including cell migration, cell invasion, path-finding of the cells, intercellular communications and so on, it has been thought that myosin X plays an important role in various processes that involve cytoskeletal reorganization including cancer progression and development of neuronal diseases. Recent studies have revealed that the unique cellular function of myosin X is closely correlated with its unique structural characteristics and motor properties. Moreover, it is found that the molecular and cellular activities of myosin X are controlled by its specific binding partner. Since recent studies have revealed the presence of various specific binding partners of myosin X, it is anticipated that the structural, biochemical and cell biological understanding of the binding partner dependent regulation of myosin X function can uncover the role of myosin X in diverse cell biological processes and diseases.

Effect of Tea Polyphenols on Conversion of Nicotine to Cotinine

  • Lee, Dong-Hee;Kim, Ha-Won
    • Biomolecules & Therapeutics
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    • v.11 no.4
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    • pp.238-244
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    • 2003
  • Nicotine is one of the major hazardous components in cigarettc smoke. Nicotine deals a harmful effect to smokers and passive smokers due to its rapid conversion to various carcinogenic metabolites. Nitrosamine-4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is believed to cause lung cancers among the nicotine-derived carcinogens. Recent studies report that NNK synthesis can be inhibited by the metabolism pathway to produce a stable metabolite cotinine from nicotine. Tea polyphenols have been known to contain factors to prevent cancers and to retard progression of cancers. This study aims to correlate tea polyphenol's potential for cancer prevention with an accelerated formation of cotinine. The conversion from nicotine to cotinine in the presence of tea extracts or three polyphenols (Catechin, epicatechin gallate, epigallocatechin gallate) was measured in established cell lines and in Xenopus oocytes. Among three lines of cell used, PLC/PRF5 and HEK293 cells showed a fast turnover from nicotine to cotinine while HepG2 cell line showed a marginal difference between groups treated and non-treated with tea polyphenols. When Xenopus oocytes were microinjected with nicotine, tea polyphenols appear to accelerate the conversion of nicotine to cotinine. Among the polyphenols tested in this study, (+)-catechin showed the best efficiency overall in accelerating conversion from nicotine to cotinine both in the cell lines and in the oocytes. In summary, the present study indicated that tea polyphenols have a positive effect on conversion of nicotine to cotinine.

Chemopreventive Effects of Ginseng on Rat Carcinogenesis

  • Wanibuchi Hideki;Ichihara Toshio;Morimura Keiichirou;Fukushima Shoji
    • Proceedings of the Ginseng society Conference
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    • 2002.10a
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    • pp.277-287
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    • 2002
  • The chemopreventive effects of ginseng on rat carcinogenesis models were investigated, In the present study, the inhibitory effects of white and red ginseng on tumor development were examined using medium-term liver, initiation and medium-term multi-organ carcinogenicity bioassay systems. No modifying potential of the ginsengs was evident in terms of the numbers or areas of glutathione S-transferase placental form (GST -P)-positive foci, which is a marker of preneoplastic lesion in rat livers. However, white ginseng, but not red ginseng was found to decrease the incidences of adenocarcinoma of the small intestine and colon in the medium-term multi-organ carcinogenesis model. These results indicate that white ginseng may have inhibitory effects on progression stage of rat intestinal carcinogenesis, but the influence is not strong. Ginseng is unlikely to have promoting or inhibitory effects in other organs under the present type of experimental conditions. Possible application on ginseng for chemoprevention of colon cancer in humans, can be concluded given the lack of obvious adverse effects.

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Multiple implant therapy with multiple inductions of general anesthesia in non-compliant patients with schizophrenia: A case report

  • Choi, Yong-suk;Kim, Hyungseok;Rhee, Seung-Hyun;Ryoo, Seung-Hwa;Karm, Myong-Hwan;Seo, Kwang-Suk;Kim, Hyun Jeong
    • Journal of Dental Anesthesia and Pain Medicine
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    • v.19 no.4
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    • pp.239-244
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    • 2019
  • The effectiveness of dental implants in patients with disability, who are non-compliant during treatment, is controversial because of their poor oral health. Thus, oral health-care and management in such patients is concerning. Moreover, limited information is available on prognosis after implant placement. Herein, we describe a patient with schizophrenia who underwent dental implantation under multiple inductions of general anesthesia (5 times) and required conservative treatment and tooth extraction for multiple dental caries and retained roots because of inadequate oral health-care. Postoperatively, fracture of the prosthodontics and progression of dental caries were observed, and with 3 additional inductions of general anesthesia, conservative treatment, implant surgery, and prosthesis implantation were conducted. Postoperative 12-month follow-up since the last prosthesis implantation showed successful results. For patients with schizophrenia, multiple implantation can reduce horizontal bone loss and achieve aesthetic results compared to treatment with removable prosthodontics and could serve as an alternative treatment modality.

Generation of knockout mouse models of cyclin-dependent kinase inhibitors by engineered nuclease-mediated genome editing

  • Park, Bo Min;Roh, Jae-il;Lee, Jaehoon;Lee, Han-Woong
    • Laboraroty Animal Research
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    • v.34 no.4
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    • pp.264-269
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    • 2018
  • Cell cycle dysfunction can cause severe diseases, including neurodegenerative disease and cancer. Mutations in cyclin-dependent kinase inhibitors controlling the G1 phase of the cell cycle are prevalent in various cancers. Mice lacking the tumor suppressors $p16^{Ink4a}$ (Cdkn2a, cyclin-dependent kinase inhibitor 2a), $p19^{Arf}$ (an alternative reading frame product of Cdkn2a,), and $p27^{Kip1}$ (Cdkn1b, cyclin-dependent kinase inhibitor 1b) result in malignant progression of epithelial cancers, sarcomas, and melanomas, respectively. Here, we generated knockout mouse models for each of these three cyclin-dependent kinase inhibitors using engineered nucleases. The $p16^{Ink4a}$ and $p19^{Arf}$ knockout mice were generated via transcription activator-like effector nucleases (TALENs), and $p27^{Kip1}$ knockout mice via clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease 9 (CRISPR/Cas9). These gene editing technologies were targeted to the first exon of each gene, to induce frameshifts producing premature termination codons. Unlike preexisting embryonic stem cell-based knockout mice, our mouse models are free from selectable markers or other external gene insertions, permitting more precise study of cell cycle-related diseases without confounding influences of foreign DNA.

Management of Chronic Kidney Disease in Obesity Patients (비만환자의 만성콩팥병 관리)

  • Han, Kunhee
    • Archives of Obesity and Metabolism
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    • v.1 no.2
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    • pp.66-73
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    • 2022
  • Obesity is an increasing public health and medical issue worldwide. It has been associated with several comorbidities, including diabetes, cardiovascular disease, stroke, and cancer. Chronic kidney disease (CKD) is another important comorbidity of obesity. Other major causes of CKD include hypertension and diabetes. However, the association between obesity and CKD is often overlooked. Among patients with CKD, patients with obesity were more vulnerable to have rapid kidney function decline than that of those with normal weight. Additionally, CKD is more prevalent among patients with obesity. These aggravations are induced through multiple mechanisms, specifically metabolic impairment of obesity and mechanical burden because of increasing intraabdominal renal pressure. Furthermore, the inflammation and lipotoxicity, caused by obesity, are critical in the CKD aggravation in patients with obesity. To prevent this, all adult patients with obesity are tested for CKD. The workup includes the estimated glomerular filtration rate and regular follow-up. Step-wise management is required for patients with obesity with CKD. Prompt reduction and management of obesity effectively delay CKD progression among patients with obesity and CKD. Therefore, weight loss is a core management for patients with obesity and CKD. Based on several studies, this article focused on the association between CKD and obesity, as well as the diagnosis and weight management of patients with obesity and CKD.