• Bulletin of the Korean Chemical Society
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• v.33 no.1
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• pp.111-114
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• 2012

Androgen receptor (AR) is ligand-inducible nuclear hormone receptor which has been focused on key molecular target in growth and progression of prostate cancer. We synthesized a series of 4-aryl 2-substituted aniline-thiazole analogs and evaluated their anti-cancer activity in AR-dependent human prostate cancer LNCap cells. Among them, the compound 6 inhibited the tumor growth in LNCap-inoculated xenograft model.

• BMB Reports
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• v.54 no.2
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• pp.112-117
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• 2021

Phospholipase D2 (PLD2) has been implicated in the tyrosine kinase-mediated signaling pathways, but the regulation events are yet to be identified. Herein, we demonstrate that pleckstrin homology (PH) domain of PLD2 (PLD2-PH) exerts an antitumorigenic effect via the suppression of PLD2 and focal adhesion kinase (FAK). The kinase domain of FAK interacts with PLD2-PH and induces tyrosine phosphorylation and activation of PLD2. Furthermore, PLD2 increased tyrosine phosphorylation of FAK. However, ectopic expression of the PLD2-PH competes for binding to FAK and reduces the interaction between PLD2 and FAK, thereby suppressing FAK-induced PLD activation and tyrosine phosphorylation of FAK. The PLD2-PH suppressed the migration and invasion of glioblastoma cells, as well as tumor formation in a xenograft mouse model. This study uncovers a novel role of PLD2-PH as a negative regulator of PLD2 and FAK.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.33 no.1
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• pp.1-9
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• 2011

Purpose: Tumor associated angiogenesis and/or lymphangiogenesis are known to be linked by VEGFR signaling pathways. These processes are regulated by several growth factors including VEGFR-2, VEGFR-3. E7080 is an orally active inhibitor of multiple tyrosine kinases including VEGFR-2, 3. Therefore, it was proposed that E7080 may inhibit angiogenesis and lymphangiogenesis. The aim of this study was to determine the effect of E7080 in a nude mouse model of OSCC. Methods: KB cells were xenografted into the submucosal tissue of the mouth floor of athymic mice. Seven days after the xenograft, the mice were randomized into 2 groups. E7080 were administered orally to the experimental group once per day. The mice were sacrificed 3 weeks after the treatment. The tumors were examined histopathologically. Immunohistochemical assays with anti- VEGF-C, VEGFR-2, VEGFR-3, phosphorylated VEGFR-2/3 (pVEGFR-2/3), and D2-40 antibodies were then performed. Results: The transplantation of human OSCC tumor cells into the mouth floor resulted in the formation of orthotopic tumors. The experimental (E7080 treatment) group showed a slowly increased tumor volume. Moreover, immunohistochemical staining demonstrated higher levels of VEGF-C, VEGFR-2, VEGFR-3, pVEGFR-2/3 and D2-40 expression in the control group than in the experimental group. Conclusion: These results suggest that E7080 may provide therapeutic benefits in OSCC.

• Journal of Ginseng Research
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• v.39 no.1
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• pp.14-21
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• 2015

Background: Colorectal cancer is a leading cause of cancer-related death, and inflammatory bowel disease is a risk factor for this malignancy. We previously reported colon cancer chemoprevention potential using American ginseng (AG) in a xenograft mice model. However, the nude mouse model is not a gut-specific colon carcinogenesis animal model. Methods: In this study, an experimental colitis and colitis-associated colorectal carcinogenesis mouse model, chemically induced by azoxymethane/dextran sodium sulfate (DSS) was established and the effects of oral AG were evaluated. The contents of representative ginseng saponins in the extract were determined. Results: AG significantly reduced experimental colitis measured by the disease activity index scores. This suppression of the experimental colitis was not only evident during DSS treatment, but also very obvious after the cessation of DSS, suggesting that the ginseng significantly promoted recovery from the colitis. Consistent with the anti-inflammation data, we showed that ginseng very significantly attenuated azoxymethane/DSS-induced colon carcinogenesis by reducing the colon tumor number and tumor load. The ginseng also effectively suppressed DSS-induced proinflammatory cytokines activation using an enzyme-linked immunosorbent assay array, in which 12 proinflammatory cytokine levels were assessed, and this effect was supported subsequently by real-time polymerase chain reaction data. Conclusion: AG, as a candidate of botanical-based colon cancer chemoprevention, should be further investigated for its potential clinical utility.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4453-4458
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• 2012

Angiogenesis plays a significant role in colorectal cancer (CRC) and cyclooxygenase-2 (COX-2) appears to be involved with multiple aspects of CRC angiogenesis. Our aim was to investigate the inhibitory effects of Tan II-A (Tanshinone II-A, Tan II-A) on tumor growth in mice, as well as alteration of expression of COX-2 and VEGF in CRC. We established the mice xenograft model of C26 CRC cell line, and injected 0.5, 1, 2mg/kg of Tan II-A and 1mg/kg of 5-FU in respectively in vivo. Then, we assayed tumor weight and volume, and evaluated microvascular density and expression of VEGF. COX-2 promoter and COX-2 plasmids were transfected into HCT-116 cells, followed by detection of COX-2 promoter activity by chemiluminescence, and detection of COX-2 mRNA expression by fluorescence quantitative PCR. Taken together, the results showed Tan II-A could inhibit tumor growth and suppress the VEGF level in vivo. HCT-116 cell experiments showed marked inhibitory effects of Tan II-A on COX-2 and VEGF in a dose-dependent manner. The results indicate that Tan II-A can effectively inhibit tumor growth and angiogenesis of human colorectal cancer via inhibiting the expression level of COX-2 and VEGF.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.9 no.1
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• pp.17-21
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• 2023

In this study, we evaluated the targeting of prostate cancer (PCa) using [¹⁸F]Florastamin in non-clinical study, for the purpose of therapeutic monitoring of [¹⁷⁷Lu]Ludotadipep, a therapeutic radiopharmaceutical for PCa, [¹⁸F]Florastamin/[¹⁷⁷Lu]Ludotadipep was co-administered to a single-individual prostate tumor bearing mouse model, mimicking clinical condition. Considering the difference in half-life of the two isotopes (¹⁸F or ¹⁷⁷Lu), image scan of whole-body autoradiography was performed at 24 or 48 h after preparation of frozen section, respectively. Then, it was confirmed whether they showed the same targeting efficiency for the area of tumor. A tumor xenograft model was prepared using PSMA-overexpressing PC3-PIP prostate cancer cells. [¹⁸F]Florastamin [111 MBq (3 mCi) in 100 µL]/¹⁷⁷Lu]Ludotadipep [3.7 MBq (100 µCi) in 100 µL] was co-administered through the tail vein, and 2 hours after administration, the mice were frozen, and after freezing for 24 hours, whole-body cryosection was performed at 24 h after freezing. Image scanning using cryosection was performed after 24 or 48 hours after freezing, respectively. In the scan image after 24 hours, tumor uptake of [¹⁸F] Florastamin/[¹⁷⁷Lu]Ludotadipep were simultaneously observed specific uptake in the tumor. In the scan image after 48 hours in the same section, signal of ¹⁸F was lost by decay of radioisotope, and specific uptake image for [¹⁷⁷Lu]Ludotadipep was observed in the tumor. Uptake of [¹⁷⁷Lu]Ludotadipep was specific to the same tumor region where [¹⁸F]Florastamin/[¹⁷⁷Lu]Ludotadipep was uptake. These results suggested that [¹⁸F]Florastamin showed the same tumor uptake efficiency to PCa as [¹⁷⁷Lu]Ludotadipep, and effective therapeutic monitoring is expected to be enable using [¹⁸F]Florastamin during [¹⁷⁷Lu]Ludotadipep therapy for PCa.

• Korean Journal of Food Science and Technology
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• v.50 no.4
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• pp.451-456
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• 2018

The current study was conducted to confirm the anti-cancer effect of Sarijang, which is a mixture of extracts from purple bamboo salt, Rhynchosia nulubilis, garlic, and Ulmi cortex. Nude mice were injected with a human-derived colorectal cancer cell (HCT116 cell line) and subsequently administered Sarijang for 4 weeks, following which the body weight, organ weight, and tumor size were measured. To evaluate the anti-cancer mechanism of Sarijang, the levels of p16 and extracellular signal-regulated kinase (ERK), cell cycle regulators in colorectal cancer, were measured. To evaluate the toxicity of Sarijang on liver and kidney, aspartate transaminase, alanine transaminase, blood urea nitrogen, and creatinine were analyzed. Sarijang not only reduced the tumor size by enhancing p16 and suppressing ERK, but also showed no side-effect in the liver and kidneys. Taken together, Sarijang has the potential to inhibit tumor growth without side effects, and may be used as a useful functional food.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.2 no.2
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• pp.108-112
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• 2016

Molecular imaging with the radiolabeled RGD peptides for ${\alpha}_v{\beta}_3$ integrin has been an increasing interest for tumor diagnosis and the treatment monitoring. Recently, $^{64}Cu$-NODAGA-gluco-E[c(RGDfK)]$_2$ was developed for quantification of ${\alpha}_v{\beta}_3$ integrin and its biological properties was elucidated. To better understand the molecular process in vivo, we performed the kinetic analysis for the $^{64}Cu$-NODAGA-gluco-E[c(RGDfK)]$_2$. After preparation of a radiotracer, dynamic PET images were obtained in the U87MG xenograft mice for 60 min (n = 6). Binding potential values were estimated from the 3-tissue compartment model, reference Logan and simplified reference tissue model. In the early time frame (0-20 min), the liver, kidney, intestine, urinary bladder and tumor were visualized but these uptakes were diminished as time went by. The tumors showed a good contrast at 40 min after administration. $^{64}Cu$-NODAGA-gluco-E[c(RGDfK)]$_2$ showed the 2-fold uptake in the tumor compared with that in the muscle. The parametric maps for binding values also provide the higher tumor-to-background contrast than the static images. A binding value obtained from the 3-tissue compartment model was comparable to other modeling methods. From these results, we conclude that $^{64}Cu$-NODAGA-gluco-E[c(RGDfK)]$_2$ may be a promising PET radiotracer for the evaluation of angiogenesis.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.409-412
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• 2013

Curcumin (Cum) has been reported to have potential chemo-preventive and chemotherapeutic activity through influencing various processes, inducing cell cycle arrest, differentiation and apoptosis in a series of cancers. However, the poor solubility of Cum limits its further applications in the treatment of cancer. We have previously reported Cum-loaded nanoparticles (Cum-NPs) prepared with amphilic methoxy poly(ethylene glycol)-polycaprolactone (mPEG-PCL) block copolymers. The current study demonstrated superior antitumor efficacy of Cum-NPs over free Cum in the treatment of lung cancer. In vivo evaluation further demonstrated superior anticancer effects of Cum-NPs by delaying tumor growth compared to free Cum in an established A549 transplanted mice model. Moreover, Cum-NPs showed little toxicity to normal tissues including bone marrow, liver and kidney at a therapeutic dose. These results suggest that Cum-NPs are effective to inhibit the growth of human lung cancer with little toxicity to normal tissues, and could provide a clinically useful therapeutic regimen. They thus merit more research to evaluate the feasibility of clinical application.

• Medical Lasers
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• v.10 no.3
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• pp.123-131
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• 2021

Optical imaging modalities with properties of real-time, non-invasive, in vivo, and high resolution for image-guided surgery have been widely studied. In this review, we introduce two optical imaging systems, that could be the core of image-guided surgery and introduce the system configuration, implementation, and operation methods. First, we introduce the optical coherence tomography (OCT) system implemented by our research group. This system is implemented based on a swept-source, and the system has an axial resolution of 11 ㎛ and a lateral resolution of 22 ㎛. Second, we introduce a fluorescence imaging system. The fluorescence imaging system was implemented based on the absorption and fluorescence wavelength of indocyanine green (ICG), with a light-emitting diode (LED) light source. To confirm the performance of the two imaging systems, human malignant melanoma cells were injected into BALB/c nude mice to create a xenograft model and using this, OCT images of cancer and pathological slide images were compared. In addition, in a mouse model, an intravenous injection of indocyanine green was used with a fluorescence imaging system to detect real-time images moving along blood vessels and to detect sentinel lymph nodes, which could be very important for cancer staging. Finally, polarization-sensitive OCT to find the boundaries of cancer in real-time and real-time image-guided surgery using a developed contrast agent and fluorescence imaging system were introduced.