• Journal of Applied Biological Chemistry
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• v.66
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• pp.379-387
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• 2023

Dog owners seek treatment when their pets develop cancer. IMMUNIES is traditional herbal medicine-based figment made of 10 natural herbs, designed to maintain host immune function. The major component of IMMUNIES is Dendropanax morbiferus. This clinical pilot study monitored the toxicity and efficacy of IMMUNIES. Four senile dogs with spontaneously occurring mammary and liver cancers were enrolled in this study and treated orally daily for 3 months, and their blood/urine biochemical profiles were examined each month. IMMUNIES was well tolerated during the treatment period. Blood urea nitrogen, creatinine, alanine aminotransferase, alkaline phosphatase, and C-reactive protein levels decreased in all four dogs, whereas red blood cells and hematocrit were within the normal range. IMMUNIES also changed the expression of several molecular targets in the anticancer pathway, such as pro-NAG-1, p53, and cyclin D1. Although the tumors did not completely respond to IMMUNIES, the biochemical profiles and clinical examination showed a stabilized cancer status for 3 months. Thus, IMMUNIES was found to be safe and well-tolerated in the dosage range tested and exhibited cancer antiproliferative activity in canine cancer. Future studies should address other potential benefits of IMMUNIES, including correlative assessments of immune function, quality of life, and owner satisfaction.

• Journal of Microbiology and Biotechnology
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• v.34 no.3
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• pp.589-595
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• 2024

Latilactobacillus curvatus BYB3 (BYB3) is a species of lactic acid bacteria, formerly named Lactobacillus curvatus, which is isolated from kimchi. In this study, the effect of BYB3, Lactobacillus rhamnosus GG, and Lactobacillus acidophilus GP1B strain extracts at various concentrations was examined on B16F10, a mouse melanoma cell line. Cell viability was examined via MTT assay, and the results indicated that compared to the other two probiotics, BYB3 significantly decreased the total percentages of viable cells. The effects of BYB3 on cell migration and proliferation in B16F10 cells were evaluated using wound healing mobility and proliferation assays, respectively; the results indicated that BYB3 inhibits cell migration and proliferation in a concentration-dependent manner. Using human dermal fibroblast cells to investigate BYB3 extract in vivo had no effect on skin-related cells. Nonetheless, the BYB3 extract inhibited tumor growth in a mouse model, as demonstrated by liver slices. Therefore, this suggests that using BYB3 extract to inhibit melanoma may be a novel approach.

• Progress in Medical Physics
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• v.9 no.3
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• pp.155-162
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• 1998

Ho-l66 was produced by neutron reaction in a reactor at the Korea Atomic Energy Institute (Taejon, Korea). Ho-l66 emits a high energy beta particles with a maximum energy of 1.85 MeV and small proportion of gamma rays (80 keV). Therefore, the radiation absorbed dose estimation could be based on the in-vivo quantification of the activity in tumors from the gamma camera images. Approximately 1 mCi of Ho-l66 in solution was mixed into the flood phantom and planar scintigraphic images were acquired with and without patient interposed between the phantom and scintillation camera. Transmission factor over an area of interest was calculated from the ratio of counts in selected regions of the two images described above. A dual-head gamma camera(Multispect2, Siemens, Hoffman Estates, IL, USA) equipped with medium energy collimators was utilized for imaging(80 keV${\pm}$10%). Fifty-nine year old female patient with hepatoma was enrolled into the therapeutic protocol after the informed consent obtained. Thirty millicuries(110MBq) of Ho-166-CHICO was injected into the right hepatic arterial branch supplying hepatoma. When the injection was completed, anterior and posterior scintigraphic views of the chest and pelvic regions were obtained for 3 successive days. Regions of interest (ROIs) were drawn over the organs in both the anterior and posterior views. The activity in those ROIs was estimated from geometric mean, calibration factor and transmission factors. Absorbed dose was calculated using the Marinelli formula and Medical Internal Radiation Dose (MIRD) schema. Tumor dose of the patient treated with 1110 MBq(30 mCi) Ho-l66 was calculated to be 179.7 Gy. Dose distribution to normal liver, spleen, lung and bone was 9.1, 10.3, 3.9, 5.0 % of the tumor dose respectively. In conclusion, tumor dose and absorbed dose to surrounding structures were calculated by daily external imaging after the Ho-l66 therapy for hepatoma. In order to limit the thresholding dose to each surrounding organ, absorbed dose calculation provides useful information.

• The Journal of Korean Society for Radiation Therapy
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• v.24 no.2
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• pp.157-165
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• 2012

Purpose: We evaluated usefulness of abdominal compressor for stereotactic body radiotherapy (SBRT) with unresectable hepatocellular carcinoma (HCC) patients and hepato-biliary cancer and metastatic liver cancer patients. Materials and Methods: From November 2011 to March 2012, we selected HCC patients who gained reduction of diaphragm movement >1 cm through abdominal compressor (diaphragm control, elekta, sweden) for HT (Hi-Art Tomotherapy, USA). We got planning computed tomography (CT) images and 4 dimensional (4D) images through 4D CT (somatom sensation, siemens, germany). The gross tumor volume (GTV) included a gross tumor and margins considering tumor movement. The planning target volume (PTV) included a 5 to 7 mm safety margin around GTV. We classified patients into two groups according to distance between tumor and organs at risk (OAR, stomach, duodenum, bowel). Patients with the distance more than 1 cm are classified as the 1st group and they received SBRT of 4 or 5 fractions. Patients with the distance less than 1 cm are classified as the 2nd group and they received tomotherapy of 20 fractions. Megavoltage computed tomography (MVCT) were performed 4 or 10 fractions. When we verify a MVCT fusion considering priority to liver than bone-technique. We sent MVCT images to Mim_vista (Mimsoftware, ver .5.4. USA) and we re-delineated stomach, duodenum and bowel to bowel_organ and delineated liver. First, we analyzed MVCT images to check the setup variation. Second we compared dose difference between tumor and OAR based on adaptive dose through adaptive planning station and Mim_vista. Results: Average setup variation from MVCT was $-0.66{\pm}1.53$ mm (left-right) $0.39{\pm}4.17$ mm (superior-inferior), $0.71{\pm}1.74$ mm (anterior-posterior), $-0.18{\pm}0.30$ degrees (roll). 1st group ($d{\geq}1$) and 2nd group (d<1) were similar to setup variation. 1st group ($d{\geq}1$) of $V_{diff3%}$ (volume of 3% difference of dose) of GTV through adaptive planing station was $0.78{\pm}0.05%$, PTV was $9.97{\pm}3.62%$, $V_{diff5%}$ was GTV 0.0%, PTV was $2.9{\pm}0.95%$, maximum dose difference rate of bowel_organ was $-6.85{\pm}1.11%$. 2nd Group (d<1) GTV of $V_{diff3%}$ was $1.62{\pm}0.55%$, PTV was $8.61{\pm}2.01%$, $V_{diff5%}$ of GTV was 0.0%, PTV was $5.33{\pm}2.32%$, maximum dose difference rate of bowel_organ was $28.33{\pm}24.41%$. Conclusion: Despite we saw diaphragm movement more than 5 mm with flouroscopy after use an abdominal compressor, average setup_variation from MVCT was less than 5 mm. Therefore, we could estimate the range of setup_error within a 5 mm. Target's dose difference rate of 1st group ($d{\geq}1$) and 2nd group (d<1) were similar, while 1st group ($d{\geq}1$) and 2nd group (d<1)'s bowel_organ's maximum dose difference rate's maximum difference was more than 35%, 1st group ($d{\geq}1$)'s bowel_organ's maximum dose difference rate was smaller than 2nd group (d<1). When applicating SBRT to HCC, abdominal compressor is useful to control diaphragm movement in selected patients with more than 1 cm bowel_organ distance.

• The Korean Journal of Nuclear Medicine Technology
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• v.14 no.1
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• pp.3-7
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• 2010

Purpose: The usefulness of Positron Emission Tomography (PET) images in diagnosis, staging, recurrent and treatment response evaluation has already been known. However, tumors which are small size, located in lower lobe of lung or upper lobe of liver are shown misalignment, distortion and different Standard Uptake Value (SUV) by respiration in PET images. Therefore, if radiotherapy based on normal respiration, it may cause low treatment response or more side effects because targets which had to treat, out of treat range or over dose to normal tissue. The purpose of this study is to evaluate attenuation-correction with Average CT (ACT) for more accuracy SUV measurement and minimize artifact by respiration. Materials and Methods: 13 patients, who had tumors which are around the diaphragm, underwent ACT scan after Helical CT (HCT) scan with PET/CT (Discovery DSTE 8; GE Healthcare). We quantified the differences between attenuation corrected image with HCT and attenuation corrected image with ACT in artifact size and maximum SUV ($SUV_{max}$). Artifacts were evaluated by measurement of the curved photogenic area in the lower thorax of the PET images for all patients. $SUV_{max}$ was measured separately at the primary tumors. Analysis program was Advantage Workstation v4.3 (GE Healthcare). Patients were injected with 7.4 MBq (0.2 $mC_i$) per kg of $^{18}F$-FDG and scanned 1 hour after injection. The PET acquisition was 3 minute per bed. Results: Significantly lower artifact were observed in PET/ACT images than in PET/HCT images (below-thoracic artifacts caused by under corrected $1.5{\pm}3.5$ cm vs. $13.4{\pm}4.2$ cm). Significantly higher $SUV_{max}$ were noted in PET/ACT images than in PET/HCT images in the primary tumor. Compared with PET/HCT images, $SUV_{max}$ in PET/ACT images were higher by $5.3{\pm}3.9%$ (mean value) tumor. The highest difference was observed in Lower lobe of lung (7.7 to 8.7; 13%). Conclusion: Due to its significantly reduced artifacts in lower thoracic, attenuation corrected image with ACT images provided more reliable $SUV_{max}$ and may be helpful in monitoring treatment response. Moreover, ACT can separate upper lobe of liver and lower lobe of lung, it may be helpful in interpretation. ACT will be clinically useful, considering increased dose caused by ACT scan and adapt.

• Radiation Oncology Journal
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• v.28 no.2
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• pp.85-90
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• 2010

Purpose: To evaluate the rate of tumor response, local control, and treatment-related complications after hypofractionated radiotherapy for recurrent hepatocelluar carcinoma (HCC) less than 5 cm in size. Materials and Methods: Among the HCC patients who were treated by radiotherapy (RT) between 2006 and 2007 after the failure of previous treatment, a total of 12 patients were treated with hypofractionated RT. The criteria for hypofractionated RT was as follows: 1) HCC less than 5 cm, 2) HCC not adjacent to a critical organ, 3) HCC without portal vein tumor thrombosis, and 4) less than 15% of normal liver volume that irradiated 50% of the prescribed dose. Hypofractionated RT was performed with 50 Gy delivered in 10 fractions, at a rate of 5 fractions per week. The evaluation of tumor response was determined by CT scans performed at 3 months after the cessation of RT, followed by the evaluation of toxicity by Common Terminology Criteria for Adverse Events version 3.0. The median follow-up period after radiotherapy was 18 months. Results: A complete response (CR) was achieved in 5 of 12 lesions (41.7%) at CT performed at 3 months after the cessation, whereas the overall complete response was observed in 7 of 12 cases (58.3%). In-field local control rate was sustained in 83.3% of patients. All patients developed intra-hepatic metastases except for 2 patients. The overall survival rate was 90.0% at 1 year and 67.5% at 2 years, respectively. Three patients developed Grade 1 nausea during RT and 1 patient showed a progression of ascites after RT. There was no grade 3 or greater treatment-related toxicities. Conclusion: Hypofractionated RT for small-sized HCC as a salvage therapy showed a 58.3% CR rate and 83.3% of local control. Fifty Gy administered in 10 fractions of partial liver irradiation is considered as a tolerable dose that does not cause severe complications.

• Progress in Medical Physics
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• v.21 no.2
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• pp.165-173
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• 2010

In this paper, we evaluated the performance of 3D CRT, IMRT and three kind of RA plannings to investigate the clinical effect of RA with liver cancer case. The patient undergoing liver cancer of small volume and somewhat constant motion were selected. We performed 3D CRT, IMRT and RA plannings such as 2RA, limited triple arcs (3RA) and 3MRA with Eclipse version 8.6.15. The same dose volume objectives were defined for only CTV, PTV and body except heart, liver and partial body in IMRT and RA plannings. The steepness of dose gradient around tumor was determined by the Normal Tissue Objective function with the same parameters in place of respective definitions of dose volume objectives for the normal organs. The approach between the defined dose constraints and the practical DVH of CTV, PTV and Body was the best in 3MRA and the worst in IMRT. The DVHs were almost the same among RAs. Plans were evaluated using Conformity Index (CI), Homogeneity Index (HI) and Quality of coverage (QoC) by RTOG after prescription with dose level surrounding 98% of PTV in the respective plans. As a result, 3MRA planning showed the better favorable indices than that of the others and achieved the lowest MUs. In this study, RA planning is a technique that is possible to obtain the faster and better dose distribution than 3D CRT or IMRT techniques. Our result suggest that 3MRA planning is able to reduce the MUs further, keeping a similar or better targer dose homogeneity, conformity and sparing normal tissue than 2RA or 3RA.

• Radiation Oncology Journal
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• v.16 no.2
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• pp.159-165
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• 1998

Purpose : The best prognosis for hepatocellular carcinoma can be achieved with surgical resection. However, the number of resected cases is limited due to the advanced lesion or associated liver disease. A trial of combined transcatheter arterial chemoembolization(TACE) and local radiotherapy(RT) for unresectable hepatocellular carcinoma(HCC) was prospectively conducted and its efficacy and toxicity were investigated. Materials and Methods : From 1992 to 1994, 30 Patients with unresectable HCC due either to advanced lesion or to associated cirrhosis were entered in the study Exclusion criteria included the presence of extrahepatic metastasis, liver cirrhosis of Child's class C, tumors occupying more than two-thirds of the whole liver, and an ECOG scale of more than 3. Patient cHaracteristics were : mean tumor size $8.95\pm3.4cm$, serum AFP+ in all patients, portal vein thrombosis in all patients, liver cirrhosis in 22 patients, and UICC stage III and IVA in 10 and 20 patients, respectively. TACE was performed with the mixture of Lipiodol(5ml) and Adriamycin(50mg) and Gelfoam embolizatin. RT(mean dose $44.0\pm9.3Gy$) 10 days with conventional fractionation. Results : An objective response was observed in 19 patients($63.3\%$). Survival rates at 1 2, and 3 years were $67\%,\;33.3\%$ and $22.2\%$, respectively. Median survival was 17 months. There were 6 patients surviving more than 3 years. Distant metastasis occurred in 10 patients, with 8 in the lung only and 2 in both lung and bone, Toxicity included transient elevation of liver function test in all patients, fever in 20, thrombocytopenia in 4, and nausea and vomiting in 1. There was no treatment-related death. Conclusion : Combined TACE and RT appear to produce a favorable response and survival results with minimal toxicity.

• Proceedings of the Ginseng society Conference
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• 2007.12a
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• pp.57-58
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• 2007

Purpose: Ginseng is a well-known medical plant used in traditional Oriental medicine. Korean red ginseng (KRG) has been known to have potent biological activities such as radical scavenging, vasodilating, anti-tumor and anti-diabetic activities. However, the mechanism of the beneficial effects of KRG on diabetes is yet to be elucidated. The present study was designed to investigate the anti-diabetic effect and mechanism of KRG extract in C57BL/KsJ db/db mice. Methods: The db/db mice were randomly divided into six groups: diabetic control group (DC), red ginseng extract low dose group (RGL, 100 mg/kg), red ginseng extract high dose group (RGH, 200 mg/kg), metformin group (MET, 300 mg/kg), glipizide group (GPZ, 15 mg/kg) and pioglitazone group (PIO, 30 mg/kg), and treated with drugs once per day for 10 weeks. During the experiment, body weight and blood glucose levels were measured once every week. At the end of treatment, we measured Hemoglobin A1c (HbA1c), blood glucose, insulin, triglyceride (TG), adiponectin, leptin, non-esterified fatty acid (NEFA). Morphological analyses of liver, pancreas and white adipose tissue were done by histological observation through hematoxylin-eosin staining. Pancreatic islet insulin and glucagon levels were detected by double-immunofluorescence staining. To elucidate an action of mechanism of KRG, DNA microarray analyses were performed, and western blot and RT-PCR were conducted for validation. Results: Compared to the DC group mice, body weight gain of PIO treated group mice showed 15.2% increase, but the other group mice did not showed significant differences. Compared to the DC group, fasting blood glucose levels were decreased by 19.8% in RGL, 18.3% in RGH, 67.7% in MET, 52.3% in GPZ, 56.9% in PIO-treated group. With decreased plasma glucose levels, the insulin resistance index of the RGL-treated group was reduced by 27.7% compared to the DC group. Insulin resistance values for positive drugs were all markedly decreased by 80.8%, 41.1% and 68.9%, compared to that of DC group. HbA1c levels in RGL, RGH, MET, GPZ and PIO-treated groups were also decreased by 11.0%, 6.4%, 18.9%, 16.1% and 27.9% compared to that of DC group, and these figure revealed a similar trend shown in plasma glucose levels. Plasma TG and NEFA levels were decreased by 18.8% and 16.8%, respectively, and plasma adiponectin and leptin levels were increased by 20.6% and 12.1%, respectively, in the RGL-treated group compared to those in DC group. Histological analysis of the liver of mice treated with KRG revealed a significantly decreased number of lipid droplets compared to the DC group. The control mice exhibited definitive loss and degeneration of islet, whereas mice treated with KRG preserved islet architecture. Compared to the DC group mice, KRG resulted in significant reduction of adipocytes. From the pancreatic islet double-immunofluorescence staining, we observed KRG has increased insulin production, but decreased glucagon production. KRG treatment resulted in stimulation of AMP-activated protein kinase (AMPK) phosphorylation in the db/db mice liver. To elucidate mechanism of action of KRG extract, microarray analysis was conducted in the liver tissue of mice treated with KRG extract, and results suggest that red ginseng affects on hepatic expression of genes responsible for glycolysis, gluconeogenesis and fatty acid oxidation. In summary, multiple administration of KRG showed the hypoglycemic activity and improved glucose tolerance. In addition, KRG increased glucose utilization and improved insulin sensitivity through inhibition of lipogenesis and activation of fatty acid $\beta$-oxidation in the liver tissue. In view of our present data, we may suggest that KRG could provide a solid basis for the development of new anti-diabetic drug.

• Journal of Nutrition and Health
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• v.55 no.2
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• pp.227-239
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• 2022

Purpose: This study investigated the effects of water-soluble mulberry leaf extract (ME) on hepatic lipid accumulation in high-fat diet-fed rats via the regulation of hepatic microRNA (miR)-221/222 and inflammation. Methods: Male Sprague-Dawley rats (4 weeks old) were randomly divided into 3 groups (n = 7 each) and fed with 10 kcal% low-fat diet (LF), 45 kcal% high-fat diet (HF), or HF + 0.8% ME for 14 weeks. Lipid profiles and cytokine levels of the liver and serum were measured using commercial enzymatic colorimetric and enzyme-linked immunosorbent assay, respectively. The messenger RNA (mRNA) and miR levels in liver tissue were assayed by real-time quantitative reverse-transcription polymerase chain reaction. Results: Supplementation of ME reduces body weight and improves the liver and serum lipid profiles as compared to the HF group. The mRNA levels of hepatic peroxisome proliferator-activated receptor-gamma, sterol regulatory element binding protein-1c, fatty acid synthase, and fatty acid translocase, which are genes involved in lipid metabolism, were significantly downregulated in the ME group compared to the HF group. In contrast, the mRNA level of hepatic carnitine palmitoyl transferase-1 (involved in fatty acid oxidation) was upregulated by ME supplementation. Furthermore, administration of ME significantly downregulated the mRNA levels of inflammatory mediators such as hepatic tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), monocyte chemoattractant protein-1, and inducible nitric oxide synthase. The serum levels of TNF-α, IL-6, and nitric oxide were also significantly reduced in ME group compared to the HF group. Expression of hepatic miR-221 and miR-222, which increase in the inflammatory state of the liver, were also significantly inhibited in the ME group compared to the HF group. Conclusion: These results indicate that ME has the potential to improve hepatic lipid accumulation in high-fat diet-fed rats via modulation of inflammatory mediators and hepatic miR-221/222 expressions.