• Tuberculosis and Respiratory Diseases
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• v.62 no.2
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• pp.125-128
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• 2007

Docetaxel is a taxoid antineoplastic drug, which is widely used to treat locally advanced or metastatic non-small cell lung cancer (NSCLC). Among the adverse dermatological reactions, nail disorders such as bending, onycholysis, hypoor hyperpigmentation are rare. We report a case of a 62-year-old male with advanced NSCLC (cT4N3M1, stage IV), who developed purulent discharge and onycholysis in the nail of all his fingers and the left great toe after five courses of anti-neoplastic chemotherapy, which included docetaxel (cumulative dose: $370mg/m^2$, 590 mg). Seven days after the final session of chemotherapy, the patient had become aware of discoloration and swelling of the nail beds with out pain. Three days later, greenish-yellow purulent discharge oozed out from the involved nails. Microbiologic studies revealed Pseudomonas aeruginosa. Intravenous and topical antibiotics (mupirocin) were applied. After 2 weeks, regrown nails were observed and the onycholysis had improved.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.29 no.1
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• pp.10-23
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• 2007

Hallmarks of clinical behaviors of adenoid cystic carcinoma(ACC) of salivary glands are the delayed onset of vascular metastasis and poor responses to classical chemotherapeutic agents. Poor prognoses from salivary ACC are caused by lung metastases that are resistant to conventional therapy. Therefore, cellular and molecular characteristics that influence the dissemination of metastatic cells are important for the design of more effective treatment of salivary ACC. Tumor angiogenesis has been known to be essential for the distant metastasis of malignant cells. So, we determined expressions of angiogenic proteins in benign (pleomorphic adenoma) and malignant (ACC, mucoepidermoid carcinoma) tumors of salivary glands and compared each other and to those in oral squamous cell carcinoma. Using surgical specimens, we performed immunohistochemical assays with anti-vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR-2), phosphorylated VEGFR-2 (pVEGFR-2), matrix metalloproteinase (MMP)-9, and interleukin (IL)-8 antibodies. Most angiogenic factors were overexpressed in malignant salivary tumors than in pleomorphic adenoma which is benign nature. Moreover, ACC demonstrated more expression of VEGFR-2 than that of squamous cell carcinoma which used as control. Conclusively, these data show those angiogenic factors produced by salivary gland tumors may affect the propagation and metastasis of malignant cells of salivary tumors, and could be used as biomarkers for the malignant transformation of salivary gland tumors. Prospectively, although further studies will be needed, these biomarkers related to angiogenesis can be molecular targets for the therapy of salivary ACC, which has propensity for delayed vascular metastasis.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.30 no.6
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• pp.529-539
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• 2008

Background and Purpose : Oral squamous cell carcinoma (OSCC) is one of the most aggressive tumors of the head and neck area. OSCC is known to preferentially metastasize via lymphatic system, and resulting cervical lymph node metastasis is the most reliable of treatment failure. But the biological mechanism of the regional nodal metastasis is not clear. So, we determined metastasis-related factors in orthotopic nude mouse models of OSCC. Experimental Design : Two cell lines-KB and YD-10B cells, established from human oral mucosal squamous cell carcinoma, were xenografted into the tissue space of athymic murine mouth floor. The mice were followed for tumor development and growth, the murine tumors were examined histopathologically for local invasion or regional or distant metastasis. Finally, we performed immunohistochemical assays with antiepithelial growth factor (EGF), EGF receptor (EGFR), phosphorylated EGFR (pEGFR), and anti-vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR)-2, phosphorylated VEGFR-2/3 (pVEGFR-2/3) antibodies. We also determined the microvessel density. Results : Transplantation of human OSCC tumor cells into the mouth floor successfully resulted in the formation of orthotopic tumors. KB cell line showed significantly higher tumor proliferation and higher nodal metastatic potential than YD-10B cell line. Furthermore, immunohistochemical staining demonstrated higher expression of EGFR/pEGFR, VEGF, and pVEGFR-2/3 as well as higher microvessel density in KB murine tumors than in YD-10B murine tumors. Conclusion : An orthotopic model of OSCC in athymic mice was established which copies the cervical lymph nodal metastasis of human OSCC. Our mouth floor model should facillitate the understanding of the molecular pathogenesis of cervical nodal metastasis of OSCC.

• YAKHAK HOEJI
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• v.48 no.3
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• pp.189-196
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• 2004

Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) playa key role in tumor invasion and metastasis. As an inhibitor of MMP-2, TIMP-2 is known to block both the invasive and metastatic behavior of cancer cells, and decrease tumor growth activity. We performed this study to investigate the effects of TIMP-2 over-expression induced by retroviral mediated gene transfer in vitro and in vivo. The human colon cancer cell line SW480 was transfected with the retroviral vector encoding TIMP-2. The effects of TIMP-2 over-expression were analyzed by invasion assay and gelatinase activity test in colon cancer cells and tumorigencity in nude mice. In evaluation of the transfection efficiency of the retroviral vector encoding TIMP-2 in colon cancer cells, we confirmed up-regulation of TIMP-2 expression dependent on the time of cell culture. In addition, inhibition of MMP-2 expression in SW480/TIMP-2 was shown by gelatin zymography. In the in vitro invasion assay SW480/TIMP-2 inhibited the invasiveness on matrigel coated with collagen. To determine whether TIMP-2 can modulate in vivo tumorigenicity and metastasis, SW480/TIMP-2 cells were injected subcutaneously in nude mice. The tumor mass formation of SW480/TIMP-2 cells in nude mice was markedly decreased compared to nontransfected cancer cells. These results showed that colon cancer cells transfected with the retroviral vector encoding TIMP-2 inhibits the invasiveness in vitro and tumorigenicity in vivo.

• Journal of Medicine and Life Science
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• v.15 no.2
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• pp.46-50
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• 2018

Cancer, a leading mortality disease following cardiovascular disease worldwide, has high incidence as one out of every four adults in Korea. It was known to be caused by several reasons including somatic mutation, activation of oncogene and chromosome aneuploidy. Cancer cells show a faster growth rate and have metastatic and heterogeneous cell populations compared to normal cells. Cancer stem cells, the most invested field in cancer biology, is a theory to explain heterogeneous cell populations of cancer cells among several characteristics of cancer cells, which is providing the theoretical background for incidence of cancer and treatment failure by drug resistance. Cancer stem cells initially explain heterogeneous cell populations of cancer cells based on the same markers of normal stem cells in cancer, in which only cancer stem cells showed heterogeneity of cancer cells and tumor initiating ability of leukemia. Based on these results, cancer stem cells were reported in various solid cancers such as breast cancer, liver cancer, and lung cancer. Breast cancer stem cells were first reported in solid cancer which had tumor initiating ability and further identified as anti-cancer drug resistance. There were several identification methods in breast cancer stem cells such as specific surface markers and culture methods. The discovery of cancer stem cells not only explains heterogeneity of cancer cells, but it also provides theoretical background for targeting cancer stem cells to complete elimination of cancer cells. Many institutes have been developing new anticancer drugs targeting cancer stem cells, but there have not been noticeable results yet. Many researchers also reported a necessity for improvement of current concepts and methods of research on cancer stem cells. Herein, we discuss the limitations and the perspectives of breast cancer stem cells based on the current concept and history.

• Development and Reproduction
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• v.25 no.2
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• pp.93-104
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• 2021

Cutaneous melanoma is a fatal disease for patients with distant metastasis. Metformin is the most widely used anti-diabetic drug, and proved to suppress cell proliferation and metastasis in diverse cancers including melanoma. We previously reported that MEK inhibitor trametinib increases the expression of epithelial-mesenchymal transition (EMT) regulators and melanoma cell motility, which are suppressed by addition of metformin in A375 melanoma cells. To confirm our findings further, we first evaluated the effect of metformin in combination with another MEK inhibitor binimetinib on cell viability in G361 melanoma cells. We then investigated whether binimetinib affects the expression of EMT regulators and cell motility. We finally monitored the effect of metformin on binimetinib-induced cell migration. Cell viability assay showed that combination index (CI) value at ED₅₀ is 0.80, suggesting synergy for the combination of metformin with binimetinib. Our results also revealed that binimetinib increased the expression of EMT regulators such as integrin αV, fibronectin and slug, which correlate well with the enhanced cell migration in wound healing assay. Metformin, on the contrary, suppressed the expression of sparc, integrin αV, fibronectin and N-cadherin with the reduced cell motility. The combination treatment showed that metformin counteracts the binimetinib-induced increase of cell motility. Overall, these results suggest that metformin with binimetinib might be useful as a potential therapeutic adjuvant against cell survival and metastatic activity in melanoma patients.

• The Journal of the Society of Stroke on Korean Medicine
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• v.12 no.1
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• pp.1-7
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• 2011

Objectives : The purpose is to discuss the clinical applications of Orungsan(Goreisan: 五苓散) as an alternative management for increased intracranial pressure in the field of neurosurgery in Japan. Methods and Results : Attention has focused on Kampo medicine(traditional Japanese medicine) for some cerebral disease including chronic subdural hematoma(CSDH) and cerebral infarction in Japan. Orungsan and one of its classes, Sirungtang(Saireto: 柴苓湯) are well known their effects on brain edema. After some studies of Orungsan has the anti-edemic effects by the inhibition of aquaporin, this herbal medicine has been used widely in the neurosurgery field in Japan. It is high time to think about where we are and we go ahead for the progress and the integration in medicine. We have reviewed the studies using Orungsan or Sirungtang, that was reported at the 20th annual meeting of 'the Japan society for Kampo medicine and neurological surgery' was held on November 5, 2011 in Tokyo. Fifteen studies related with Orungsan or Sirungtang were reported among all 32 studies at the meeting. Orungsan in ten, and Sirungtang in five among 14 studies contained specific clinical case. In the aspects of disease, thirteen papers were related with SDH, including CSDH(11), SSDH(1), aneurism clipping for SDH prevention(1), and one was acute cerebral infarction and one was multiple metastatic brain tumor. In the report style, case control study was 7(mostly retrospective), and the case report was 8. Conclusions : Orungsan may be plausible to be an alternative method to reduce brain edema after SDH and other brain injury in the field of neurosurgery.

• Nuclear Medicine and Molecular Imaging
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• v.40 no.1
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• pp.9-15
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• 2006

Purpose: Previous studies have not showed consistent results for the level of expression of sodium/iodide symporter (NIS) in thyroid diseases, especially malignant tumor. We undertook this study to evaluate the distribution of NIS expression in malignant thyroid diseases and compare with that in benign thyroid disease. Materials and Methods: Total patients were 119 cases (Men 15, $48{\pm}13$ yrs). Total number of samples were 205 pieces. In malignant thyroid disease, there were 153 samples: 90 in papillary carcinoma, 4 in follicular carcinoma, 2 in medullary carcinoma and 57 in metastatic lymph node. In benign thyroid disease, there were 52 samples: 36 in goiter/cyst, 11 in thyroiditis and 5 in follicular adenoma. Using immunohistochemical methods, we probed 205 samples with monoclonal anti-NIS Ab. Grading of staining was stored as 0 (negative or absent), 1 (weakly positive), 2 (moderately positive) or 3 (strongly positive). Expression rate (ER) of NIS positivity in individual disease entity was expressed as percentage of total number divided by number in 2 plus 3 grade. Results: ERs of malignant thyroid diseases were 63% in papillary carcinoma, 81% in metastatic lymph node, 71% in follicular carcinoma and 100% in medullary carcinoma. ERs of benign thyroid disease were 53% in goiter/cyst, 64% in thyroiditis and 40% in follicular adenoma. ER of malignant thyroid diseases was higher than benign thyroid diseases (71% vs 54%). Grading of NIS expression in papillary carcinoma or goiter/cyst was heterogeneously distributed in considerable cases. Normal tissue also showed heterogeneous distribution of NIS expression, which was not correlated with that of primary lesion. Conclusion: In papillary thyroid carcinoma, distribution of NIS expression was heterogeneous and increased, and not different compared with that of benign thyroid disease.

• Journal of Korean Ophthalmic Optics Society
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• v.7 no.1
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• pp.39-43
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• 2002

This study was investigated the anti-angiogenic activities of Cnidium officinale Makino and Tabanus bovinus by using Chorioallantoic membrane (CAM) and rat cornea. First experiment, the fertilized chicken eggs were kept in a humidified egg incubator at $37^{\circ}C$. After 4 days incubation, about 3 ml of albumin was aspirated from eggs with an hypodermic needles through a small hole drilled at the narrow end of the eggs, and the shell membrane on the floor of the air sac was peeled away. Embryos with chorioallantois of 3~5 mm in diameter were employed for the assay of antiangiogenic activity. Retinoic acid was used as a positive control for this experiment. After 48 h of treatment. branching pattern of blood vessels below coverslip containing retinoic acid ($10{\mu}g/egg$) was dramatically decreased. A simiar angiogenic inhibition was observed in the CAM treated with $50{\mu}g/egg$ of Cnidium omcinale Makino and Tabanus bovinus extracts. Second experiment, rat corneal neovascularization was induced by suturing (one stitch) the cornea with 10-0 nylon, and terramycin was applied on the cornea for I week to prevent corneal inflammation. In the cornea of rats untreated with herbal extracts, numerous vessels were usually seen invading the cornea by day 2 or 3 after suture, and reaching the lesion area within 5~6 days. Corneal neovascularization was gradually increased and peaked at 3 weeks. In contrast to this, herbal extracts conspicuously inhibited the angiogenesis, Oral administration of herbal extracts (20 mg/kg body weight/day) for 4 weeks significantly inhibited the rat corneal angiogenesis induced by suture, and the length of blood vessels in herbal medicine-treated rat cornea was conspicuously lower than that in control animals. A similar phenomenon was also observed in the rat cornea treated with thalidomide (200 mg/kg body weight/day). These findings indicate the anti-angiogenic properties of Cnidium officinale Makino and Tabanus bovinus, suggesting that these properties may be one of the pharmacological mechanisms underlying the anti-tumor and anti-metastatic activities of herbal extracts tested in this study.

• The Korean Journal of Food And Nutrition
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• v.25 no.4
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• pp.941-950
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• 2012

In order to develop new physiologically active polysaccharides from persimmon leaves, two different crude polysaccharides were prepared using hot water (PLW-0) and pectinase digestion (PLE-0) and their immuno-stimulating activities were estimated. PLW-0 and PLE-0 showed similar sugar compositions with 15 different sugars, including rarely observed sugars in general polysaccharides such as 2-O-methyl-fucose, 2-O-methyl-xylose, apiose, aceric acid, 3-deoxy-D-manno-2-octulosonic acid, and 3-deoxy-D-lyxo-2-heptulosaric acid, but the uronic acid content of PLE-0 was lower than that of PLW-0 caused by pectinase treatment. Both PLW-0 and PLE-0 showed potent anti-complementary activity in a dose-dependent manner which was similar to a known immuno-stimulating polysaccharide, PSK, from Coriolus versicolor. The activity of PLE-0 at a low concentration ($100{\mu}g/m{\ell}$) was higher than that of PLW-0. In an in vitro cytotoxicity analysis, PLW-0 and PLE-0 (up to $1,000{\mu}g/m{\ell}$) did not affect the growth of peritoneal macrophages and Colon 26-M3.1 carcinoma cells. In contrast, they enhanced lymphocyte proliferation activity. Peritoneal macrophages stimulated with PLW-0 and PLE-0 produced various cytokines, such as IL-6 and IL-12. However, PLE-0 was more effective on the cytokine production. Intravenous administration of PLW-0 and PLE-0 significantly augmented natural killer (NK) cell cytotoxicity against Yac-1 tumor cells 3 days after the treatment of polysaccharide fractions. But NK cells obtained from the PLE-treated group showed higher tumoricidal activity even at a low dose of $40{\mu}g$/mouse. In experimental lung metastasis of Colon 26-M3.1 carcinoma cells, prophylactic administration of PLW-0 and PLE-0 significantly inhibited lung metastasis in a dose-dependent manner and PLE-0 was more effective on the inhibition of cancer metasasis. The results lead us to conclude that the pectinase-treated process is indispensable to preparing polysaccharides with higher immune-stimulating activity from persimmon leaves.