• Biomolecules & Therapeutics
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• 제30권2호
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• pp.162-169
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• 2022

We utilized Fas21, a resveratrol analog, to modulate the function of hepatic stellate cells (HSCs) and liver sinusoidal endothelial cells (LSECs) during the angiogenic phase of murine liver metastasis by B16 melanoma and 51b colorectal carcinoma. Preangiogenic micrometastases were treated with Fas21 (1 mg/kg/day) or vehicle during the development of intra-angiogenic tracts. Mice treated with Fas21 showed reduced liver tumor foci in both liver metastasis models. Micrometastases were classified immunohistochemically, as well as according to their position coordinates and connection to local microvasculature. The volume of liver occupied by sinusoidal-type foci, containing infiltrating angiogenic capillaries, decreased by ~50% in Fas21-treated mice compared to vehicle-treated ones in both tumor metastasis models. The volume of portal foci, containing peripheral neoangiogenesis within a discontinuous layer of myofibroblasts, was similar in all experimental groups in both tumor metastasis models, but displayed enhanced necrotic central areas devoid of angiogenesis following Fas21 treatment. As a result, sinusoidal tumors from mice treated with Fas21 showed a 50% reduction in desmin(+)/asma(+) HSCs and CD31(+) vessel density, and a 45% reduction in intrametastatic VEGF mRNA compared with sinusoidal tumors from vehicle-treated mice. Necrotic portal metastases increased 2-4-fold in treated mice. In vitro, Fas21 reduced VEGF secretion by HSCs and 51b cells dose-dependently. Additionally, HSCs migration in response to tumor soluble factors was dose-dependently diminished by Fas21, as was LSEC migration in response to HSCs and tumor soluble factors. Resveratrol analog Fas21 inhibits the proangiogenic response of HSCs and LSECs during the development of murine liver metastasis.

• Asian Pacific Journal of Cancer Prevention
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• 제15권2호
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• pp.703-706
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• 2014

Objective: To evaluate the safety and efficacy of sequential transcatheter arterial chemoembolization (TACE) and portal vein embolization (PVE) before major hepatectomy for patients with hepatocellur carcinoma (HCC). Methods: In this retrospective case-control study, data were collected from patients who underwent sequential TACE and PVE prior to major hemihepactectomy. Liver volumes were measured by computed tomography volumetry before TACE, and preoperation to assess degree of future remnant liver (FRL) hypertrophy and to check whether intro- or extrohepatic metastasis existed. Liver function was monitored by biochemistry after TACE, prior to and after major hepatectomy. Results: Mean average FRL volume increased 32.3-71.4% (mean 55.4%) compared with preoperative FRL volume. After TACE, liver enzymes were elevated, but returned to normal in four weeks. During PVE and resection, no patient had intro- or extrohepatic metastasis. Conclusion: Sequential TACE and PVE is an effective method to improve resection opportunity, expand the scope of surgical resection, and greatly reduce postoperative intra- and extrahepatic metastasis.

• Radiation Oncology Journal
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• 제34권1호
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• pp.64-75
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• 2016

Purpose: In order to evaluate the relationship between the dose to the liver parenchyma and focal liver reaction (FLR) after stereotactic ablative body radiotherapy (SABR), we suggest a novel method using a three-dimensional dose distribution and change in signal intensity of gadoxetate disodium-gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) hepatobiliary phase images. Materials and Methods: In our method, change of the signal intensity between the pretreatment and follow-up hepatobiliary phase images of Gd-EOB-DTPA-enhanced MRI was calculated and then threshold dose (TD) for developing FLR was obtained from correlation of dose with the change of the signal intensity. For validation of the method, TDs for six patients, who had been treated for liver cancer with SABR with 45-60 Gy in 3 fractions, were calculated using the method, and we evaluated concordance between volume enclosed by isodose of TD by the method and volume identified as FLR by a physician. Results: The dose to normal liver was correlated with change in signal intensity between pretreatment and follow-up MRI with a median $R^2$ of 0.935 (range, 0.748 to 0.985). The median TD by the method was 23.5 Gy (range, 18.3 to 39.4 Gy). The median value of concordance was 84.5% (range, 44.7% to 95.9%). Conclusion: Our method is capable of providing a quantitative evaluation of the relationship between dose and intensity changes on follow-up MRI, as well as determining individual TD for developing FLR. We expect our method to provide better information about the individual relationship between dose and FLR in radiotherapy for liver cancer.

• 대한의용생체공학회:의공학회지
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• 제43권6호
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• pp.434-440
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• 2022

Liver transplantation is a critical used treatment method for patients with end-stage liver disease. The number of cases of living donor liver transplantation is increasing due to the imbalance in needs and supplies for brain-dead organ donation. As a result, the importance of the accuracy of the donor's suitability evaluation is also increasing rapidly. To measure the donor's liver volume accurately is the most important, that is absolutely necessary for the recipient's postoperative progress and the donor's safety. Therefore, we propose liver segmentation in abdominal CT images from pre-operation, POD 7, and POD 63 with a two-dimensional U-Net. In addition, we introduce an algorithm to measure the volume of the segmented liver and measure the hepatectomy rate and regeneration rate of pre-operation, POD 7, and POD 63. The performance for the learning model shows the best results in the images from pre-operation. Each dataset from pre-operation, POD 7, and POD 63 has the DSC of 94.55 ± 9.24%, 88.40 ± 18.01%, and 90.64 ± 14.35%. The mean of the measured liver volumes by trained model are 1423.44 ± 270.17 ml in pre-operation, 842.99 ± 190.95 ml in POD 7, and 1048.32 ± 201.02 ml in POD 63. The donor's hepatectomy rate is an average of 39.68 ± 13.06%, and the regeneration rate in POD 63 is an average of 14.78 ± 14.07%.

• 대한방사선치료학회지
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• 제13권1호
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• pp.14-22
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• 2001

Purpose: The aim of this study is to investigate geometrical and volumetrical changes of liver due to breathing and its impact to NTCP. In order to attain better treatment results it should be considered deliberately during planning session. Mehtods and Materials : Seven patients were examined in this study who have done TACE for accurate tumor margin drawing. After contrast media injection, C-T scan data were obtained in supine position during breathing free, inhalation and exhalation, respectively. For all patients C-T scan were done with same scanning parameters- 5 mm index, 5 mm thickness and pitch 1. Based on C-T data we have measured differences of each variables between breathing status such as changes of total and remained liver volumes, GTV, beam path length and superior to inferior shift. NTCP were calculated using Lyman's effective volume DVH reduction scheme and for this NTCP calculation, the V50 was computed from DVH and each m, n value were referred from Burmans data. Results : The measured total tilter volume and the remained liver volume changed between inspiration and expiration about $1.2-7.7\%(mean+2.7\%)$ and $2.5-13.23\%(mean=5.8\%)$ respectively, and these results were statistically significant(p>0.1). The GTV difference in each patient varied widely from $1.17\%\;to\;30.69\%$, but this result was not statistically significant. Depending on the breathing status, the beam path length was changed from 0.5 cm to 1.1 cm with the average of 0.7 cm, and it was statistically significant(p=0.006). The measured superior to inferior shifts were ranged from 0.5 cm to 3.74 cm. The NTCPs were changed relatively small in each patient, but the variation was large between the patients. The mean NTCP difference was $10.5\%$, with the variation ranged from $7\%\;to\;23.5\%$. Conclusion : Variations of liver volume and of beam path length were changed significantly depending on the breathing statues and the range of variation itself was very different between the patients. Since this variance could seriously affect the clinical outcomes of radiation treatments, the breathing of patients need to be accounted when a final treatment planning is derided.

• Asian Pacific Journal of Cancer Prevention
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• 제14권5호
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• pp.3045-3050
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• 2013

Purpose: Hepatic resection is arguably the preferred treatment for huge hepatocellular carcinoma (H-HCC). Estimating the remnant liver volume is therefore essential. This study aimed to evaluate the feasibility of using computer-assisted volumetric analysis for this purpose. Methods: The study involved 40 patients with H-HCC. Laboratory examinations were conducted, and a contrast CT-scan revealed that 30 cases out of the participating 40 had single-lesion tumors. The remaining 10 had less than three satellite tumors. With the consensus of the team, two physicians conducted computer-assisted 3D segmentation of the liver, tumor, and vessels in each case. Volume was automatically computed from each segmented/labeled anatomical field. To estimate the resection volume, virtual lobectomy was applied to the main tumor. A margin greater than 1 cm was applied to the satellite tumors. Resectability was predicted by computing a ratio of functional liver resection (R) as (Vresected-Vtumor)/(Vtotal-Vtumor) x 100%, applying a threshold of 50% and 60% for cirrhotic and non-cirrhotic cases, respectively. This estimation was then compared with surgical findings. Results: Out of the 22 patients who had undergone hepatectomies, only one had an R that exceeded the threshold. Among the remaining 18 patients with non-resectable H-HCC, 12 had Rs that exceeded the specified ratio and the remaining 6 had Rs that were < 50%. Four of the patients who had Rs less than 50% underwent incomplete surgery due to operative findings of more extensive satellite tumors, vascular invasion, or metastasis. The other two cases did not undergo surgery because of the high risk involved in removing the tumor. Overall, the ratio of functional liver resection for estimating resectability correlated well with the other surgical findings. Conclusion: Efficient pre-operative resectability assessment of H-HCC using computer-assisted volumetric analysis is feasible.

• 한국임상수의학회지
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• 제28권4호
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• pp.357-364
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• 2011

To evaluate hepatoprotective effect of Epimedium Koreanum nakai (EKN) on liver-damaged animal model, rats were intoxicated with carbon tetrachloride (1 ml/kg) for 9 weeks orally. Liver-damaged rats were divided into 2 groups: liver-damaged control (LDC) group and EKN group were administered vehicle (saline), EKN extract per os for 4 weeks respectively. Normal control (NC) group was administered saline as the same process of LDC group. The weights of prostate (absolute), testis (relative), epididymis (relative) and packed cell volume (PCV), mean corpuscular volume (MCV) of EKN group significantly (P < 0.05) increased compared with LDC group. But Mean corpuscular hemoglobin (MCH), mean corpusulcar hemoglobin concentration (MCHC) and aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) were significantly (P < 0.01, P < 0.05) decreased. Fibrotic regions in hepatic parenchyma of EKN group significantly (P < 0.01) decreased compared with LDC group and mean diameters of hepatic lobules significantly (P < 0.01) increased. Percentages of degenerative kidney regions and number of degenerative kidney tubules, number of vasodilated atrophic glomerulus of EKN group was significantly (P < 0.01, P < 0.05) decreased compared with LDC group. Number of atrophic seminiferous tubules and epididymal tubules showing oligospermatozoa of EKN group were significantly (P < 0.01) decreased compared with LDC group. In conclusion, EKN extract has a favorable effect on the $CCl_4$-induced liver damage.

• 대한수의학회지
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• 제34권2호
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• pp.249-258
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• 1994

This study was carried out to investigate the inhibitory effects of vitamin E on the oxidative damage of cellular lipids and proteins in free radical reaction induced by $FeCl_3$, and ascorbic acid. In this experiment, a vitamin E treated rat group was administered with 100mg/kg body weight of $dl-{\alpha}-tocophery$ 1 acetate and an untreated rat group was administered with the same volume of corn oil. And then assays of malondialdehyde and carbonyl group in total homogenate, mitochondrial and microsomal fraction of rat liver were carried out at the scheduled time. The results obtained from this study were summarized as follows; 1. Lipid peroxidation levels in vitamin E administered rat liver cells were significantly (p<0.05) decreased at the intervals between 1 hour and 4 hours in liver homogenate, at all times except for 1 hour point in mitochondrial fraction, and also at the intervals between 0.5 hour and 3 hours in microsomal fraction compared with those of the control rat liver cell. 2. Protein oxidation levels in vitamin E administered rat liver cell were also significantly (p<0.05) decreased at the intervals between 1.5 hours and 4 hours in liver homogenate, at over 4 hours in liver mitochondrial fraction, and at the intervals between 0.5 hour and 3 hours in liver microsomal fraction compared with those of the control rat liver cells.

• 한국대기환경학회지
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• 제13권3호
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• pp.207-214
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• 1997

We collected airborne complex mixtures in a industrial area of Yeochun, and examined whether these complex mixtures could affect gap junctional intercellular communication (GJIC) in a cultured WBF-344 rat liver epithelial cells (LEC). Since the reduction of GJIC plays an important role in chemical carcinogenesis, measurement of changes of GJIC is a meaningful method to screen carcinogenicity of these mixtures. High and low volume samples were dissolved in dimethyl sulfoxide (DMSO) and tested. Blank filter extractions were also examined for exclud-ing possible toxicity of filter itself, and TPA (12-O-tetradecanoylphorbol-13-acetate) and DMSO were used as positive and negative control, respectively. When the cells were exposed to samples at concentration below that required to maintain rather than 85% cell viability based on the result of neutral red uptake assay, maximal inhibition of GJIC was observed at 1hr after treatment with both high and low volume samples by scrape-loading dye transfer assay. In fluorescence recovery after photobleaching assay, recovery rates via gap junctions were 33%/min in high volume sample and 62%/min in low volume sample. In together, airborne samples collected in Yeochun inhibited GJIC in a cultured WBF-344 rat LEC. These results suggest airborne samples tested in this experiment may attribute to cause a certain type and degree of cancers in in vivo when exposured for some periods.

• Archives of Pharmacal Research
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• 제12권2호
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• pp.68-72
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• 1989

The hydrolysis rates of ester and amide derivatives of 20-dihydroprednisolonic acid were measured in rat serum and liver homogenate. The hydrolysis rate of the esters in serum was found to be faster than that in liver homogenate on the basis of blood volume and liver weight, while the amide derivatives showed much slower change. And it is also found that the size of substituents at C-21 and C-20 configuration expressed considerable effects on the hydrolysis rate of these derivatives.