• Radiation Oncology Journal
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• v.34 no.1
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• pp.1-9
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• 2016

Overexpression of human epidermal growth factor receptor 2 (HER2) is found in about 20% of breast cancer patients. With treatment using trastuzumab, an anti-HER2 monoclonal antibody, systemic control is improved. Nonetheless, the incidence of brain metastasis does not be improved, rather seems to be increased in HER2-positive breast cancer. The mainstay treatment for brain metastases is radiotherapy. According to the number of metastatic lesions and performance status of patients, radiosurgery or whole brain radiotherapy can be performed. The concurrent use of a radiosensitizer further improves intracranial control. Due to its large molecular weight, trastuzumab has a limited ability to cross the blood-brain barrier. However, small tyrosine kinase inhibitors such as lapatinib, has been noted to be a promising agent that can be used as a radiosensitizer to affect HER2-positive breast cancer. This review will outline general management of brain metastases and will focus on preclinical findings regarding the radiosensitizing effect of small molecule HER2 targeting agents.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.137.2-137.2
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• 2003

Dendritic cells (DCs) are known to professional antigen presenting cell (APC). Due to the role as an effective activator of cytotoxic T Lymphocytes by expressing MHC, adhesion and co-stimulatory molecules, DCs are now widely recognized to play an important role in the immune responses to tumors.We investigated the effect of cultured DCs in murine melanoma pulmonary metastasis model. To follow the metastasis protocol, syngenic melanoma cells were inoculated intra-venously into the mouse (B16F10 into the C57BL/6)8 days prior to the first DC injection (1$\times$106 DCs/ mouse, i.p.) and the autologous tumor cell lysate pulsed-DCs were injected as a therapeutic module twice in two weeks. (omitted)

• International Journal of Oral Biology
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• v.49 no.2
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• pp.42-47
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• 2024

Ophiopogonin D (OPD) is a steroidal glycoside derived from Ophiopogon japonicus, a traditional Chinese medicine with diverse biological activities, including antithrombosis, anti-inflammation, and antitussive effects. To investigate the cellular effects and mechanisms of OPD on oral squamous cell carcinoma, cell viability was explored, and the effects of OPD on cell cycle regulators, apoptotic marker proteins, and key proteins involved in metastasis and signaling pathways were examined by MTT assay and Western blotting in YD38 cells. OPD strongly inhibited cell proliferation and induced caspase-dependent apoptosis of YD38 cells by suppressing the cell cycle and activating caspase-3 and poly ADP ribose polymerase. Additionally, OPD suppressed the expression of vital proteins regulating metastasis and proliferation within the integrin/matrix metalloproteinases/FAK and AKT/PI3K/mTor pathways. Thus, OPD can be a potential treatment candidate for gingival cancer.

• Herbal Formula Science
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• v.31 no.4
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• pp.295-313
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• 2023

Objectives : While treatments for cancer are advancing, the development of effective treatments for cancer metastasis, the main cause of cancer patient death, remains insufficient. Recent studies on Dichroae Radix have revealed that its active ingredients have the potential to inhibit cancer metastasis. This study aimed to investigate the cancer metastasis inhibitory effect of Dichroae Radix using network pharmacological analysis. Methods : The active compounds of Dichroae Radix have been identified using Traditional Chinese Medicine System Pharmacology Database and Analysis Platform. The UniProt database was used to collect each of information of all target proteins associated with the active compounds. To find the bio-metabolic processes associated with each target, the DAVID6.8 Gene Functional classifier tool was used. Compound-Target and Target-Pathway networks were analyzed via Cytoscape 3.40. Results : In total, 25 active compounds and their 62 non-redundant targets were selected through the TCMSP database and analysis platform. The target genes underwent gene ontology and pathway enrichment analysis. The gene list applied to the gene ontology analysis revealed associations with various biological processes, including signal transduction, chemical synaptic transmission, G-protein-coupled receptor signaling pathways, response to xenobiotic stimulus, and response to drugs, among others. A total of eleven genes, including HSP90AB1, CALM1, F2, AR, PAKACA, PTGS2, NOS2, RXRA, ESR1, ESR2, and NCOA1, were found to be associated with biological pathways related to cancer metastasis. Furthermore, nineteen of the active compounds from Dichroae Radix were confirmed to interact with these genes. Conclusions : The results provide valuable insights into the mechanism of action and molecular targets of Dichroae Radix. Notably, Berberine, the main active ingredient of Dichroae Radix, plays a significant role in degrading AR proteins in advanced prostate cancer. Further studies and validations can provide crucial data to advance cancer metastasis prevention and treatment strategies.

• Molecules and Cells
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• v.39 no.5
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• pp.403-409
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• 2016

NME1 is a well-known metastasis suppressor which has been reported to be downregulated in some highly aggressive cancer cells. Although most studies have focused on NME1, the NME1 gene also encodes the protein (NME1L) containing N-terminal 25 extra amino acids by alternative splicing. According to previous studies, NME1L has potent anti-metastatic activity, in comparison with NME1, by interacting with $IKK{\beta}$ and regulating its activity. In the present study, we tried to define the role of the N-terminal 25 amino acids of NME1L in $NF-{\kappa}B$ activation signaling. Unfortunately, the sequence itself did not interact with $IKK{\beta}$, suggesting that it may be not enough to constitute the functional structure. Further construction of NME1L fragments and biochemical analysis revealed that N-terminal 84 residues constitute minimal structure for homodimerization, $IKK{\beta}$ interaction and regulation of $NF-{\kappa}B$ signaling. The inhibitory effect of the fragment on cancer cell migration and $NF-{\kappa}B$-stimulated gene expression was equivalent to that of whole NME1L. The data suggest that the N-terminal 84 residues may be a core region for the anti-metastatic activity of NME1L. Based on this result, further structural analysis of the binding between NME1L and $IKK{\beta}$ may help in understanding the anti-metastatic activity of NME1L and provide direction to NME1L and $IKK{\beta}$-related anti-cancer drug design.

• The Korean Journal of Food And Nutrition
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• v.23 no.2
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• pp.141-146
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• 2010

Cisplatin(cis-diamminedichloroplatium) is one of the most effective anti-cancer drugs being clinically used in the treatment of solid tumors. Despite its therapeutic benefits, its use in clinical practice is often limited because of dose related toxicity. It is known that yeast cell wall beta-glucans possess immuno-modulating properties, which allows for their application in antitumor therapy. IS2 is a kind of beta-glucan derived from the cell wall of mutated Saccharomyces cerevisiae, which exhibits anti-cancer activity in vitro and in vivo. The present study explored the possibility of combination therapy of IS2 with cisplatin. In experimental metastasis of colon26-M3.1 cells, prophylactic intravenous administration of IS-2 in combination with cisplatin effectively inhibited tumor metastasis compared with cisplatin alone or IS-2 treatment in vivo. IS-2 effectively enhanced Th1 type cytokines including IFN-$\gamma$, IL-2, IL-12 and GM-CSF. Simultaneously, this combined treatment inhibited production of Th2 type cytokines compared with control. These results suggested that IS-2 can be applied in combination therapy with anti-cancer drugs to minimize their side effects.

• Asian Pacific Journal of Cancer Prevention
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• v.18 no.11
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• pp.2919-2923
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• 2017

Objective: Anthocyanins belong to a class of flavonoids, exhibiting antioxidant and anti-inflammatory actions have been reported to have anti-cancer effects. Here, we investigated whether anthocyanins can inhibit cancer cell proliferation, invasion, and angiogenesis in human lung cancer A549 cells, which are critically involved in cancer metastasis. Methods: We used anthocyanins from fruits of Vitis coignetiae Pulliat (AIMs) which has been used in Korean folk medicine for the treatment of inflammatory diseases and cancers. We have performed cell proliferation assays, cell invasion assay, gelatin zymography, wound healing assay and western blotting to examine whether anthocyanins can inhibit cancer cell proliferation, invasion, and angiogenesis in A549 cells. Result: AIMs did not inhibit cancer cell proliferation on A549 cells. Also, AIMs suppressed cancer migration, and invasion by supressing MMP-2 and MMP-9 expression. The Immuno-blotting results also revealed that AIMs suppressed the proteins involved in cancer proliferation (COX-2, C-myc, cyclin D1), migration and invasion (MMP-2, MMP-9), anti-apoptosis (XIAP, and c-IAP2), adhesion and angiogenesis (ICAM-1, VEGF). Conclusion: This study demonstrates that the anthocyanins isolated from fruits of Vitis coignetiae Pulliat inhibit cancer proliferation, cancer migration, and invasion that is involve in cancer-metastasis. This study provides evidence that AIMs might have anti-cancer effects on human lung cancer.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.5
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• pp.1363-1369
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• 2005

Previously we have shown that shikonin has strong anti-tumor activities via inducing apoptosis and suppressing metastasis on LLC cells in vivo and in vitro. Here we have investigated anti-angiogenic potential of shikonin and its possible mechanism of action in HSE cells. Shikonin inhibited the proliferation of HSE cells in a concentration-dependent manner. It was shown that this proliferation inhibition was caused by apoptosis induced by shikonin via BrdU incorporation and Western blotting analysis. Shikonin treatment was caused that decrease of activation of caspases and cleavage of PARP. And shikonin induced that the activation of mitogen-activated protein kinases (MAPKs), such as extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38. Moreover, shikonin showed anti-angiogenic activities inhibiting tube-like formation of HSE cells in vitro and vascular formation of LLC cells in vivo. These findings suggest that shikonin may a possible candidate not only anti-metastatic agent but also anti-angiogenic agent.

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.10a
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• pp.139-140
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• 2001

Ginseng saponins (ginsenosides) have been regarded as principal components responsible for the majority of pharmacological activities exerted by ginseng. IH-901, an intestinal bacterial metabolite derived from the protopanaxadiol saponin of Panax ginseng C.A. Meyer, has been reported to have anti-tumor effects including inhibition of angiogenesis, invasion and metastasis, as well as induction of tumor cell apoptosis. (omitted)

• Advances in Traditional Medicine
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• v.5 no.4
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• pp.283-293
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• 2005

Our previous study showed that a novel synthetic shikonin derivative, 6-(1-hydroxyimino-4-methylpentyl)5,8-dimethyoxy 1,4-naphthoquinone S-52 (DMNQ S-52) induced apoptosis. In the present study, we investigated its anti-metastatic activities as compared with shikonin because DMNQ S-52 was synthesized for overcoming weak points of shikonin such as high toxicity, low solubility and deleterious effects. DMNQ S-52 showed the weaker cytotoxicity $(IC_{50};\;12.3{\pm}1.6\;{\mu}M)$ against Lewis lung carcinoma (LLC) cells than that of shikonin $(IC_{50};\;4.2{\pm}1.1\;{\mu}M)$. DMNQ S-52, at non-toxic concentrations $(less\;than\;10\;{\mu}M)$, significantly inhibited the invasion and migration of LLC cells. DMNQ S-52 also significantly inhibited the production of MMP-9, MTl-MMP and uPAR. Moreover, daily i.p. administration of DMNQ S-52 at dose of 5 mg/kg in mice resulted in a potent inhibition of the primary tumor size of LLC in the lung as well as the metastasis of lymph nodes. These findings suggest that the DMNQ S-52 has therapeutic potential to inhibit metastasis via inhibition of MMP family and uPA/plasminogen system.