• 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.

• Proceedings of the KSLP Conference
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• 2011.03a
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• pp.14-14
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• 2011

• Maxillofacial Plastic and Reconstructive Surgery
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• v.38
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• pp.29.1-29.9
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• 2016

Background: The objective of this study was to evaluate xenograft degradation velocity when treated with 4-hexylresorcinol (4HR). Methods: The scapula of a cow was purchased from a local grocery, and discs (diameter 8 mm, thickness 1 mm) were prepared by trephine bur. Discs treated with 4HR were used as the experimental group. Untreated discs were used as the control. X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), antibacterial test, endotoxin test, and scanning electron microscopy (SEM) were performed on the discs. In vivo degradation was evaluated by the rat calvarial defect model. Results: The XRD and FT-IR results demonstrated successful incorporation of 4HR into the bovine bone. The experimental disc showed antibacterial properties. The endotoxin test yielded results below the level of endotoxin contamination. In the SEM exam, the surface of the experimental group showed needle-shaped crystal and spreading of RAW264.7 cells. In the animal experiments, the amount of residual graft was significantly smaller in the experimental group compared to the control group (P = 0.003). Conclusions: In this study, 4HR was successfully incorporated into bovine bone, and 4HR-incorporated bovine bone had antibacterial properties. In vivo experiments demonstrated that 4HR-incorporated bovine bone showed more rapid degradation than untreated bovine bone.

• Journal of Ginseng Research
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• v.36 no.1
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• pp.86-92
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• 2012

The glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults. Despite combination treatments of radiation and chemotherapy, the survival periods are very short. Therefore, this study was conducted to assess the potential of ginsenoside $F_2$ (F2) to treat GBM. In in vitro experiments with glioblastoma cells U373MG, F2 showed the cytotoxic effect with $IC_{50}$ of 50 ${\mu}g/mL$ through apoptosis, confirmed by DNA condensation and fragmentation. The cell population of cell cycle sub-G1 as indicative of apoptosis was also increased. In xenograft model in SD rats, F2 at dosage of 35 mg/kg weight was intravenously injected every two days. This reduced the tumor growth in magnetic resonance imaging images. The immunohistochemistry revealed that the anticancer activity might be mediated through inhibition of proliferation judged by Ki67 and apoptosis induced by activation of caspase-3 and -8. And the lowered expression of CD31 showed the reduction in blood vessel densities. The expression of matrix metalloproteinase-9 for invasion of cancer was also inhibited. The cell populations with cancer stem cell markers of CD133 and nestin were reduced. The results of this study suggested that F2 could be a new potential chemotherapeutic drug for GBM treatment by inhibiting the growth and invasion of cancer.

• Molecules and Cells
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• v.42 no.11
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• pp.755-762
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• 2019

Despite decades of research into colorectal cancer (CRC), there is an ongoing need for treatments that are more effective and safer than those currently available. Lactic acid bacteria (LAB) show beneficial effects in the context of several diseases, including CRC, and are generally regarded as safe. Here, we isolated a Lactobacillus rhamnosus (LR)-derived therapeutic protein, p8, which suppressed CRC proliferation. We found that p8 translocated specifically to the cytosol of DLD-1 cells. Moreover, p8 down-regulated expression of Cyclin B1 and Cdk1, both of which are required for cell cycle progression. We confirmed that p8 exerted strong anti-proliferative activity in a mouse CRC xenograft model. Intraperitoneal injection of recombinant p8 (r-p8) led to a significant reduction (up to 59%) in tumor mass when compared with controls. In recent years, bacterial drug delivery systems (DDSs) have proven to be effective therapeutic agents for acute colitis. Therefore, we aimed to use such systems, particularly LAB, to generate the valuable therapeutic proteins to treat CRC. To this end, we developed a gene expression cassette capable of inducing secretion of large amounts of p8 protein from Pediococcus pentosaceus SL4 (PP). We then confirmed that this protein (PP-p8) exerted anti-proliferative activity in a mouse CRC xenograft model. Oral administration of PP-p8 DDS led to a marked reduction in tumor mass (up to 64%) compared with controls. The PP-p8 DDS using LAB described herein has advantages over other therapeutics; these advantages include improved safety (the protein is a probiotic), cost-free purification, and specific targeting of CRC cells.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7057-7063
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• 2013

The discovery of the immunodeficient mice has provided a tool for establishing animal models as hosts for in vivo analysis of AML. Various model systems have been established in the last few decades, and it is essential that murine AML models are developed to exploit more specific, targeted therapeutics. In this review, we concentrate on the models of AML and discuss the development of immunodeficiency models for understanding of leukemogenesis, describe those now available and their values and document the methods used for establishing and identifying AML mice models, as well as factors influencing engraftment of human AML in immunodeficient mice. Thus, the function of this article is to provide clinicians and experimentalists with a chronological, comprehensive appraisal of all AML model systems.

• Journal of Chest Surgery
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• v.25 no.10
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• pp.1041-1047
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• 1992

The consecutive 35 patients underwent isolated aortic valve replacement with the low-profile model of the Ionescu-Shiley pericardial xenograft valve from 1984 to 1991. Operative mortality was 2.9%, and early survivors were followed up for a total 136.1 patient-years[Mean$\pm$SD, 4.00$\pm$2.14 years]. The linearized late mortality was 2.204% /pt-yr. Three patients required rereplacement of the valve with overall valve failure rate of 2.204% /pt-yr: two for endocarditis and one for paravalvular leak. There was no case of primary tissue failure. The linearized annual rates of complication were: thromboembolism 0.735% /pt-yr, bleeding 0.735%pt-yr, and endocarditis 2.204% /pt-yr. The actuarial survival at 8 years of follow-up was 90.4$\pm$5.3%, and the probabilities of freedom from thromboembolism and from rereplacement were 95.6$\pm$4.4% and 88.2$\pm$6.7% at 8 years respectively. Although the low profile Ionescu-Shiley pericardial valve provided favorable clinical performance comparable with the standard model up to 8 years, it needs prolonged follow-up to assess the pattern of its durability.

• BMB Reports
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• v.57 no.8
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• pp.352-362
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• 2024

Hematopoietic stem cell transplantation (HSCT) remains an indispensable therapeutic strategy for various hematological diseases. This review discusses the pivotal role of bone marrow (BM) niches in influencing the efficacy of HSCT and evaluates the current animal models, emphasizing their limitations and the need for alternative models. Traditional animal models, mainly murine xenograft, have provided significant insights, but due to species-specific differences, are often constrained from accurately mimicking human physiological responses. These limitations highlight the importance of developing alternative models that can more realistically replicate human hematopoiesis. Emerging models that include BM organoids and BM-on-a-chip microfluidic systems promise enhanced understanding of HSCT dynamics. These models aim to provide more accurate simulations of the human BM microenvironment, potentially leading to improved preclinical assessments and therapeutic outcomes. This review highlights the complexities of the BM niche, discusses the limitations of current models, and suggests directions for future research using advanced model systems.

• Food Science and Preservation
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• v.23 no.1
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• pp.104-109
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• 2016

The purpose of this study was to evaluate the inhibitory effect of commercial Makgeolli on tumor growth in human gastric adenocarcinoma cells (AGS) in a xenograft cancer model, transplanted with AGS cells. Commercial Makgeolli was first dealcoholized by evaporation and used as the test sample. We detected a significant increase in the volume and weight of tumor in nude mice (induction) that were transplanted with AGS cells. Administration of $100mg/kg{\cdot}day$ group (ML), and $500mg/kg{\cdot}day$ group (MH) dealcoholized commercial Makgeolli significantly decreased tumor growth. In this study, 5-FU $18mg/kg{\cdot}day$ was used as a positive control for tumor growth inhibition. Additionally, determination of the body weight of both the groups revealed no side effects after the administration of dealcoholized commercial Makgeolli. Using the cell culture system, we also evaluated the effect of dealcoholized commercial Makgeolli on caspase-3/7 activity in the AGS cells. Treatment with dealcoholized commercial Makgeolli increased the activation of caspase-3/7 and the apoptotic markers in AGS cells in a dose-dependent manner. Therefore, dealcoholized commercial Makgeolli can be used for cancer prevention.

• Journal of Chest Surgery
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• v.47 no.4
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• pp.333-343
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• 2014

Background: A preclinical study was conducted for evaluating a valved conduit manufactured with a glutaraldehyde (GA)-fixed bovine pericardium treated using an anticalcification protocol. Methods: Bovine pericardia were decellularized, fixed with GA in an organic solvent, and detoxified. We prepared a valved conduit using these bovine pericardia and a specially designed mold. The valved conduit was placed under in vitro circulation by using a mock circulation model, and the durability under mechanical stress was evaluated for 2 months. The valved conduit was implanted into the right ventricular outflow tract of a goat, and the hemodynamic, radiologic, histopathologic, and biochemical results were obtained for 6 months after the implantation. Results: The in vitro mock circulation demonstrated that valve motion was good and that the valved conduit had good gross and microscopic findings. The evaluation of echocardiography and cardiac catheterization demonstrated the good hemodynamic status and function of the pulmonary xenograft valve 6 months after the implantation. According to specimen radiography and a histopathologic examination, the durability of the xenografts was well preserved without calcification at 6 months after the implantation. The calcium and inorganic phosphorus concentrations of the explanted xenografts were low at 6 months after the implantation. Conclusion: This study demonstrated that our synergistic employment of multiple anticalcification therapies has promising safety and efficacy in the future clinical study.