• The Korean Journal of Nuclear Medicine
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• v.30 no.3
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• pp.344-350
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• 1996

Purpose : Noninvasive imaging of tumor cell proliferation could be helpful in the evaluation of tumor growth potential and could provide an early assessment of treatment response. Radiolabeled thymidine, uridine and adenosine have been used to evaluate tumor cell proliferation. These nucleoside analogs are incorporated into DNA during proliferation. Iodine-131-Iodomethyluridine, an analog of Iodine-131-Iododeoxyuridine, is also involved in DNA/RNA synthesis. The purpose of this study was to develop Iodine-131-Iodomethylurdine and image tumor proliferation using Iodine-131-Iodomethyluridine. Materials and Methods : Radiosynthesis of Iodine-131-5-Iodo-2'-O-methyluridine (Iodine-131-Iodomethyluridine) was prepared from 10 mg of 2'-O-methyluridine(Sigma chemical Co., St. Louis, Missouri) and 2.1 mCi(SP. 10Ci/mg) of Iodine-131-labeled sodium iodide in $100{\mu}l$ of water using iodogen reaction. Female Fischer 344 rats were inoculated in the thigh area with breast tumor cells(13765 NF, $10^5$ cells/rat S.C.). After 14 days, the Iodine-131-Iodomethyluridine $10{\mu}Ci$ was injected to three groups of rats(3/group). The percent of injected dose per gram of tissue weight was determined at 0.5-hours, 2-hours, 4-hours, and 24-hours respectively. Tumor bearing rats after receiving Iodine-131-Iodomethyluridine($50{\mu}Ci$ IV) were euthanized at 2 hours after injection. Autoradiography was done using freeze-dried $50{\mu}m$ coronal section. After injection of Iodine-131- Iodomethyluridine ($10{\mu}Ci$/rat, IV) in three breast tumor-bearing rats, planar scintigraphy was taken at 45 minutes, 90 minutes and 24 hours. Results : Iodine-131-Iodomethyluridine was conveniently synthesized using iodogen reaction. The biodistribution showed fast blood clearance and the tumor-to-tissue uptake ratios showed that optimal imaging time was at 2 hours postinjection. Autoradiogram and planar scintigram indicated that tumor could be well visualized. Conclusion : The findings suggest that Iodine-131-Iodomethyluridine, a new radio-iodinated nucleoside, has potential use for evaluation of active regions of tumor growth.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.22 no.2
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• pp.39-49
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• 2009

Objective : Phyllostachyos Folium (PF) has been used to treat patients with febrile disease consuming the body fluids marked by fever with restlessness, thirst etc. In the theory of herbology, PF can clear away heat and promote the production of the body fluids, relieve restlessness. Recently PF is known to have anti-bacterial, anti-oxidantic effects. Methods : The present study was carried out to investigate the effects of PF on solid tumor in mice in terms of immune-potentiating and direct cytotoxic action of PF in vitro and vivo study. The present author investigated thymocyte and splenocyte proliferation to confirm immune-potentiating activity of PF and also investigated tumor/body weight ratio and survival rates in tumor bearing mice. Result : In this study, administration of PF decreased tumor/body weight ratio significantly, and prolonged survival duration compared to non-treated control. In addition, treatment with PF suppressed proliferation rate of Sarcoma 180 (S-180) cells significantly, and elevated proliferation rates of thymocytes isolated from normal mice. These results were co-related with in vivo study. Conclusion : In conclusion, these results suggest that PF is useful to treat patient with solid tumor, because PF has direct toxic action for tumor cell and immune -potentiating action for T cells. Further study will need to elucidate exact mechanisms related in anti-cancer action of PF.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.6
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• pp.1404-1408
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• 2003

The combined effects of water-soluble fraction of Moschus (ME) and anti-tumor drug mitomycin C on the proliferation of human tumor cell-lines were estimated by MTT colorimetric assay. ME inhibited the proliferation of Hep G2, A540, HeLa, KHOS-NP and Balb/c 3T3 cells. Also, ME increased the cytotoxicity of mitomycin C on Hep G2, A549 and HeLa cells. In addition, ME enhanced the cell viability of murine splenocytes and human lymphocytes at the concentration of 100㎍/㎖. These results indicate that ME inhibits the proliferation of human tumor cells and increases the cytotoxicity of mitomycin C without cytoxicity on immune cells.

• Archives of Pharmacal Research
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• v.22 no.4
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• pp.348-353
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• 1999

Possible antiinflammatory effect of eudesmin were examined by assessing the effects on tumor necrosis factor (TNF)-$\alpha$ production and lymphocyte proliferation as well as cytotoxicity against murine and human macrophages. the compound significantly inhibited TNF-$\alpha$, production by lipopolysaccaride (LPS)-stimulated murine macrophage RAW264.7 without displaying cytotoxicity suggesting that eudesmin may inhibit TNF-$\alpha$ production without any interference of normal cell function. It also significantly attenuated T cell proliferation stimulated by concanavalin A (Con A) in a dose-dependent manner.

• The Korean Journal of Nuclear Medicine
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• v.36 no.4
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• pp.209-223
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• 2002

By considering the biological properties of a tumor, it should be possible to realize better results in cancer therapy. PET imaging offers the opportunity to measure tumor growth non-invasively and repeatedly as an early assessment of response to cancer therapy. Measuring cellular growth instead of energy metabolism showed offer significant advantages in evaluating therapy. Thymidine and its derivative nucleoside compounds can be changed to mono, di- and tri- phosphate compounds by thymidine kinase and then be incorporated into DNA. Their bindings are increased in highly proliferating cells due to the high DNA synthesis rate. To evaluate cell proliferation, many kinds of thymidine and uridine derivatives have been labeled with positron emitter and radioactive iodine. Compared to radiopharmaceuticals which have radioisotope labeled base ring such as pyirmidine, the radiopharmacuticals which have radioisotope labeled sugar ring are more stable in vivo and have metabolic resistance. The biological properties such as DNA incorporation ratios are highly dependent on their chemical structures and metabolic processes. This overview describes synthesis of radiopharmaceuticals and their biological properties for imaging of tumor cell proliferation.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.15
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• pp.6349-6352
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• 2014

The present study was undertaken to determine the roles of insulin in the growth of transplanted breast cancer in nude mice, and the proliferation and migration of MCF-7 human breast cancer cells and assess its influence on downstream signaling pathways. In a xenograft mouse model with injection of MCF-7 human breast cancer cells, tumor size was measured every other day. The insulin level and insulin receptor (IR) were increased in the breast cancer patient tissues. Insulin injected subcutaneously around the tumor site in mice caused increase in the size and weight of tumor masses, and promoted proliferation and migration of MCF-7 cells. The effects of insulin on the increase in the proliferation and migration of MCF-7 human breast cancer cells were abolished by pretreatment with the extracellular regulated kinase (ERK) inhibitor PD98059. Insulin increased the phosphorylation of ERK in the MCF-7 cells. These results indicate that insulin promotes the growth of breast cancer in nude mice, and increases the proliferation and migration of MCF-7 human breast cancer cells via the ERK pathway.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.35 no.2
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• pp.66-73
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• 2009

Tumor angiogenesis is a process leading to formation of blood vessels within tumors and is crucial for maintaining a supply of oxygen and nutrients to support tumor growth and metastasis. Vascular endothelial growth factor(VEGF) plays a key role in tumor angiogenesis including induction of endothelial cell proliferation, migration, survival and capillary tube formation. VEGF binds to two distinct receptors on endothelial cells. VEGFR-2 is considered to be the dominant signaling receptor for endothelial cell permeability, proliferation, and differentiation. Bevacizumab(Avastin, Genetech, USA) is a monoclonal antibody against vascular endothelial growth factor. It is used in the treatment of cancer, where it inhibits tumor growth by blocking the formation of new blood vessels. The goal of this study is to identify the anti-tumor effect of Bevacizumab(Avastin) for oral squamous cell carcinoma cell lines. Human squamous cell carcinoma cell line(HN4) was used in this study. We examined the sensitivity of HN4 cell line to Bevacizumab(Avastin) by using in vitro proliferation assays. The results were as follows. 1. In the result of MTT assay according to concentration of Bevacizumab(Avastin), antiproliferative effect for oral squamous cell carcinoma cell lines was observed. 2. The growth curve of cell line showed the gradual growth inhibition of oral squamous cell carcinoma cell lines after exposure of Bevacizumab(Avastin). 3. In the apoptotic index, groups inoculated Bevacizumab(Avastin) were higher than control groups. 4. In condition of serum starvation, VEGFR-2 did not show any detectable autophosphorylation, whereas the addition of VEGF activated the receptor. Suppression of phosphorylated VEGFR-2 and phosphorylated MAPK was observed following treatment with Bevacizumab(Avastin) in a dose-dependent manner. 5. In TEM view, dispersed nuclear membrane, scattered many cytoplasmic vacuoles and localized chromosomal margination after Bevacizumab(Avastin) treatment were observed. These findings suggest that Bevacizumab(Avastin) has the potential to inhibit MAPK pathway in proliferation of oral squamous cell carcinoma cell lines via inhibition of VEGF-dependent tumor growth.

• Molecules and Cells
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• v.39 no.12
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• pp.847-854
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• 2016

The early landmark discoveries in cancer metabolism research have uncovered metabolic processes that support rapid proliferation, such as aerobic glycolysis (Warburg effect), glutaminolysis, and increased nucleotide biosynthesis. However, there are limitations to the effectiveness of specifically targeting the metabolic processes which support rapid proliferation. First, as other normal proliferative tissues also share similar metabolic features, they may also be affected by such treatments. Secondly, targeting proliferative metabolism may only target the highly proliferating "bulk tumor" cells and not the slowergrowing, clinically relevant cancer stem cell subpopulations which may be required for an effective cure. An emerging body of research indicates that altered metabolism plays key roles in supporting proliferation-independent functions of cancer such as cell survival within the ischemic and acidic tumor microenvironment, immune system evasion, and maintenance of the cancer stem cell state. As these aspects of cancer cell metabolism are critical for tumor maintenance yet are less likely to be relevant in normal cells, they represent attractive targets for cancer therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.11
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• pp.4509-4513
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• 2015

Osteosarcoma is the most common primary bone tumor in humans, especially in childhood. However, the genetic etiology for its pathogenesis remains elusive. It is known that microRNAs (miRNAs) are involved in the development of tumor progression. Here we show that microRNA-9 (miR-9) is a potential oncogene upregulated in osteosarcoma cells. Knockdown of miR-9 in osteosarcoma resulted in suppressed colony formation and cell proliferation. Further study identified GCIP, a Grap2 and cyclin D interacting protein, as a direct target of miR-9. In addition, GCIP overexpression activated retinoblastoma 1 (Rb) and suppressed E2F transcriptional target expression in osteosarcoma cells. Moreover, GCIP depletion reversed miR-9 knockdown induced colony formation and cell proliferation suppression. In sum, these results highlight the importance of miR-9 as an oncogene in regulating the proliferation of osteosarcoma by directly targeting GCIP and may provide new insights into the pathogenesis of osteosarcoma.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.769-773
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• 2015

Fibulin-5 has recently been considered as a potential tumor suppressor in human cancers. Several studies have shown that it is down-regulated in a variety of tumor types and inhibits tumor growth and metastasis. This study was aimed to investigate the clinical significance of fibulin-5 in glioma and its role in cell proliferation and invasion. We found that the expression of fibulin-5 in glioma tissues was significantly lower than those in normal brain (NB) tissues. Negative expression was significantly correlated with advanced clinical stage (grade III+IV). Furthermore, Fibulin-5 negative expression was correlated with a shorter overall survival of glioma patients. Multivariate Cox repression analysis indicated that fibulin-5 was an independent factor for predicting overall survival of glioma patients. Overexpression obviously inhibited cell proliferation in U251 and U87 cells. Furthermore, it significantly reduced the number of migrating and invading glioma cells. In conclusion, impaired expression of fibulin-5 is correlated with the advanced tumor stage in glioma. Otherwise, Fibulin-5 is an independent prognostic marker for predicting overall survival of glioma patients. Mechanistically, it may function as a tumor suppressor via inhibiting cell proliferation and invasion in gliomas.