• Molecules and Cells
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• v.21 no.2
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• pp.213-217
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• 2006

Although AIMP1 (previously known as p43) is one of three auxiliary proteins bound to a macromolecular aminoacyl tRNA complex, it is also secreted as a cytokine controlling both angiogenesis and immune responses. Here we show that systemically administered purified recombinant human AIMP1 had anti-tumor activity in mouse xenograft models. In Meth A-bearing Balb/c mice, tumor volume increased about 28 fold in the vehicle treatment group, while an increase of about 16.7 fold was observed in the AIMP1-treated group. We also evaluated the anti-tumor activity of AIMP1 in combination with a sub-clinical dose of the cytotoxic anti-tumor drug, paclitaxel. The growth of NUGC-3 human stomach cancer cells was suppressed by 84% and 94% by the combinations of 5 mg/kg paclitaxel + 25 mg/kg AIMP1 (p = 0.03), and 5 mg/kg paclitaxel + 50 mg/kg AIMP1 (p = 0.02), respectively, while 5 mg/kg paclitaxel alone suppressed growth by only 54% (p = 0.02). A similar cooperative effect of AIMP1 and paclitaxel was observed in a lung cancer xenograft model. These results suggest that AIMP1 may be useful as a novel anti-tumor agent.

• BMB Reports
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• v.56 no.12
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• pp.669-674
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• 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to various clinical symptoms including anemia. Lipocalin-2 has various biological functions, including defense against bacterial infections through iron sequestration, and it serves as a biomarker for kidney injury. In a human protein array, we observed increased lipocalin-2 expression due to parental SARS-CoV-2 infection in the Calu-3 human lung cancer cell line. The secretion of lipocalin-2 was also elevated in response to parental SARS-CoV-2 infection, and the SARS-CoV-2 Alpha, Beta, and Delta variants similarly induced this phenomenon. In a Calu-3 implanted mouse xenograft model, parental SARSCoV-2 and Delta variant induced lipocalin-2 expression and secretion. Additionally, the iron concentration increased in the Calu-3 tumor tissues and decreased in the serum due to infection. In conclusion, SARS-CoV-2 infection induces the production and secretion of lipocalin-2, potentially resulting in a decrease in iron concentration in serum. Because the concentration of iron ions in the blood is associated with anemia, this phenomenon could contribute to developing anemia in COVID-19 patients.

• Journal of Pharmacopuncture
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• v.19 no.2
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• pp.114-121
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• 2016

Objectives: Lung cancer remains a deadly disease with unsatisfactory overall survival. Cisplatin, a standard platinum (Pt)-based chemotherapeutic agent, has the potential to inhibit the growth of lung cancer. Its use, however, is occasionally limited by severe organ toxicity. However, until now, no systematic study has been conducted to verify its efficacy with proper experimental support in vivo. Therefore, we examined whether biosynthesized Pt nanoparticles (NPs) inhibited human lung cancer in vitro and in vivo to validate their use in alternative and complementary medicine. Methods: We evaluated the in vitro and the in vivo anticancer efficiencies of biosynthesized Pt NPs in a subcutaneous xenograft model with A549 cells. Severe combined immune deficient mice (SCID) were divided into four groups: group 1 being the vehicle control group and groups 2, 3 and 4 being the experimental groups. Once the tumor volume had reached $70-75mm^3$, the progression profile of the tumor growth kinetics and the body weights of the mice were measured every week for 6 weeks after oral administration of Pt NPs. Doses of Pt NPs of 500, 1,000 and 2,000 mg/kg of body weight were administered to the experimental groups and a dose of honey was administered to the vehicle control group. The efficacy was quantified by using the delay in tumor growth following the administration of Pt NPs of A549 human-lung-cancer xenografts growing in SCID mice. Results: The in vitro cytotoxicity evaluation indicated that Pt NPs, in a dose-dependent manner, inhibited the growth of A549 cells, and the in vivo evaluation showed that Pt NPs at the mid and high doses effectively inhibited and delayed the growth of lung cancer in SCID mice. Conclusion: These findings confirm the antitumor properties of biosynthesized Pt NPs and suggest that they may be a cost-effective alternative for the treatment of patients with lung cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6463-6468
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• 2012

Purpose: To evaluated the effect of the gambogic acid (GA), one of the effective components of Garcinia, in combination with a new multi-targeted oral medication, sunitinib (SU) on renal cancer cell proliferation in vitro and on tumor growth in vivo. Methods: After treatment with GA or SU, either alone or in combination, MTT and FACS analysis were used to examine cell viability and cycle distribution of the renal carcinoma cell lines 786-0 and Caki-1. Western blotting was employed to examine the expression of proteins related to the cell cycle and vascular formation. Furthermore, a xenograft model was applied to study the antitumor efficacy of SU or GA alone or in combination, with immunohistochemistry to detect expression of proteins related to xenograft growth and angiogenesis. Western blotting was used to examine NF-${\kappa}B$ signaling pathway elements in xenografts. Results: Treatment of 786-0 and Caki-1 cells with GA or SU resulted in decreased tumor cell proliferation, especially with joint use. Cells accumulated more strongly in the sub-G1 phase after joint treatment with GA and SU than treatment of GA and SU alone. Western blotting arrays showed 1 protein significantly upregulated, 2 proteins downregulated, and 2 proteins unchanged. Moreover, combined use of GA and SU inhibited the growth and angiogenesis of xenografts generated from Caki-1 significantly. Immunohistochemistry arrays showed downregulation of the expression of proteins promoting xenograft growth and angiogenesis, and Western blotting showed inhibition of the NF-${\kappa}B$ signaling pathway after treatment by GA alone and in combination with SU in xenografts. Conclusions: Our results show that the joint use of GA and SU can provide greater antitumor efficacy compared to either drug alone and thus may offer a new treatment strategy for renal cell carcinoma.

• Journal of Ginseng Research
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• v.41 no.3
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• pp.386-391
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• 2017

Background: Korean Red Ginseng (KRG) is an ethnopharmacological plant that is traditionally used to improve the body's immune functions and ameliorate the symptoms of various diseases. However, the antitumorigenic effects of KRG and its underlying molecular and cellular mechanisms are not fully understood in terms of its individual components. In this study, in vitro and in vivo antitumorigenic activities of KRG were explored in water extract (WE), saponin fraction (SF), and nonsaponin fraction (NSF). Methods: In vitro antitumorigenic activities of WE, SF, and NSF of KRG were investigated in the C6 glioma cell line using cytotoxicity, migration, and proliferation assays. The underlying molecular mechanisms of KRG fractions were determined by examining the signaling cascades of apoptotic cell death by semiquantitative reverse transcriptase polymerase chain reaction and Western blot analysis. The in vivo antitumorigenic activities of WE, SF, and NSF were investigated in a xenograft mouse model. Results: SF induced apoptotic death of C6 glioma cells and suppressed migration and proliferation of C6 glioma cells, whereas WE and NSF neither induced apoptosis nor suppressed migration of C6 glioma cells. SF downregulated the expression of the anti-apoptotic gene B-cell lymphoma-2 (Bcl-2) and upregulated the expression of the pro-apoptotic gene Bcl-2-associated X protein (BAX) in C6 glioma cells but had no effect on the expression of the p53 tumor-suppressor gene. Moreover, SF treatment resulted in activation of caspase-3 as evidenced by increased levels of cleaved caspase-3. Finally, WE, SF, and NSF exhibited in vivo antitumorigenic activities in the xenograft mouse model by suppressing the growth of grafted CT-26 carcinoma cells without decreasing the animal body weight. Conclusion: These results suggest that WE, SF, and NSF of KRG are able to suppress tumor growth via different molecular and cellular mechanisms, including induction of apoptosis and activation of immune cells.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.737-741
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• 2014

Background: In recent years a wide variety of flavonoids or polyphenolic substances have been reported to possess substantial anti-carcinogenic and antimutagenic activities. Grape proanthocyanidins (GPC) are considered as good examples for which there is evidence of potential roles as anti-carcinogenic agents. Methods: A xenograft model was established using H22 cells subcutaneously injected into mice and used to assess different concentrations of grape proanthocyanidins (GPC) and Endostar. Treatments were maintained for 10 days, then levels of vascular endothelial growth factor (VEGF) and microvessel density (MVD) were examined by immunohistochemistry, while VEGF mRNA was determined by real-time PCR in tumor tissue. Results: The expression of MVD and VEGF decreased gradually as the concentration of GPC increased.There was a significant positive correlation between MVD and VEGF. Conclusions: These results suggest that GPC restrains the growth of tumor, possibly by inhibiting tumour angiogenesis.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.35 no.4
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• pp.199-204
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• 2009

Purpose: The purpose of this study is to investigate the epithelial-mesenchymal transition (EMT) induced by Snail transcription factor and Snail-transfected in vivo tumors with histopathological features. Materials and methods: We induced in vivo xenografted tumorigenesis in the oral vestibules of nude mice by a Snail transfected HaCaT cell line and investigated morphological and immunohistochemical features in Snail expressive tumors. Results: We identified tumor masses in 14 out of 15 nude mice in the HaCaT-Snail cell inoculation group, but no tumors were present in any of the HaCaT cell inoculation group. Induced tumors showed features of poorly differentiated carcinoma with invasion to neighboring muscles and bones. The HaCaT-Snail tumors showed decreased expressions of E-cadherin and cytokeratin, but showed increased expressions of vimentin and N-cadherin. Discussion: The Snail transfected xenograft can improve productivity of malignant tumors, show various histopathological features including invasive growth, and aid in the investigation of tumor progression and the interaction with surrounding tissues.

• Archives of Plastic Surgery
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• v.48 no.4
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• pp.433-439
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• 2021

Acellular dermal matrices (ADM) are a novel graft. The goal of this systematic review is to evaluate the evidence behind differences in human and porcine ADM, irrelevant of manufacturing method, and to determine if there is enough of an evidence base to change clinical practice. An extensive literature search was performed through MEDLINE and Embase with search terms defining a population, intervention and outcome. Title and abstract exclusion were performed with other exclusion criteria. In 191 articles were found after exclusion of duplicates, with only 29 remaining following exclusions. Ten studies were found to have level I and II evidence (I=3, II=8), of which two were histopathological, one was an animal model, one was a systematic review, and six were clinical. The remaining studies were reviewed and considered for discussion, but did not hold high enough standards for medical evidence. Strong clinical evidence already exists for the use of human ADM, but questions of access, cost, and ethics require consideration of a xenograft. Histopathologically, evidence suggests minimal long-term differences between human and porcine ADM, although there is a short acute immune response with porcine ADM. Clinically, there is limited difference in outcomes, with a small range in effect of different ADM preparations. Considering the effectiveness of ADM in wound healing, more high-level research with appropriate statistical analysis to facilitate a future meta-analysis is recommended to justify a transition from human to porcine ADM.

• Biomolecules & Therapeutics
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• v.30 no.2
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• pp.151-161
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• 2022

This study elucidates the anti-cancer potential of gallic acid (GA) as a promising therapeutic agent that exerts its effect by regulating the PI3K/Akt pathway. To prove our research rationale, we used diverse experimental methods such as cell viability assay, colony formation assay, tumor spheroid formation assay, cell cycle analysis, TUNEL assay, Western blot analysis, xenograft mouse model and histological analysis. Treatment with GA inhibited cell proliferation in dose-dependent manner as measured by cell viability assay at 48 h. GA and cisplatin (CDDP) also inhibited colony formation and tumor spheroid formation. In addition, GA and CDDP induced apoptosis, as determined by the distribution of early and late apoptotic cells and DNA fragmentation. Western blot analysis revealed that inhibition of the PI3K/Akt pathway induced upregulation of p53 (tumor suppressor protein), which in turn regulated cell cycle related proteins such as p21, p27, Cyclin D1 and E1, and intrinsic apoptotic proteins such as Bax, Bcl-2 and cleaved caspase-3. The anti-cancer effect of GA was further confirmed in an in vivo mouse model. Intraperitoneal injection with GA for 4 weeks in an A549-derived tumor xenograft model reduced the size of tumor mass. Injection of them downregulated the expression of proliferating cell nuclear antigen and p-Akt, but upregulated the expression of cleaved caspase-3 in tumor tissues. Taken together, these results indicated that GA hindered lung cancer progression by inducing cell cycle arrest and apoptosis, suggesting that GA would be a potential therapeutic agent against non-small cell lung cancer.

• Anatomy and Cell Biology
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• v.57 no.1
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• pp.97-104
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• 2024

Heavy reliance on glucose metabolism and a reduced capacity to use ketone bodies makes glioblastoma (GBM) a promising candidate for ketone-based therapies. Ketogenic diet (KD) is well-known for its promising effects in controlling tumor growth in GBM. Moreover, synthetic ketone ester (KE) has demonstrated to increase blood ketone levels and enhance animal survival in a metastatic VM-M3 murine tumor model. Here, we compared the efficacy of a KE-supplemented Atkins-type diet (ATD-KE) to a classic KD in controlling tumor progression and enhancing survival in a clinically relevant orthotopic patient-derived xenograft GBM model. Our findings demonstrate that ATD-KE preserves body weight (percent change from the baseline; 112±2.99 vs. 116.9±2.52 and 104.8±3.67), decreases blood glucose (80.55±0.86 vs. 118.6±9.51 and 52.35±3.89 mg/dl), and increases ketone bodies in blood (1.15±0.03 mM vs. 0.55±0.04 and 2.66±0.21 mM) and brain tumor tissue (3.35±0.30 mM vs. 2.04±0.3 and 4.25±0.25 mM) comparable to the KD (results presented for ATD-KE vs. standard diet [STD] and KD, respectively). Importantly, the ATD-KE treatment significantly enhanced survival compared to the STD and was indistinguishable from the KD (47 days in STD vs. 56 days in KD and ATD-KE), suggesting that a nutritionally balanced low carbohydrate ATD combined with KE may be as effective as the KD alone in reducing brain tumor progression. Overall, these data support the rationale for clinical testing of KE-supplemented low-carb diet as an adjunct treatment for brain tumor patients.