Background: The high recurrence rate after hepatic resection in hepatocellular carcinoma (HCC) is a major obstacle to improving prognosis. The objective of the present study was to explore the function of genistein, a soy-derived isoflavone, in enhancing the inhibitory effect of cisplatin on HCC cell proliferation and on tumor recurrence and metastasis in nude mice after curative hepatectomy. Methods: Proliferation of human HCC cells (HCCLM3) was detected by 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay. Synergistic effects of genistein and cisplatin were evaluated with the median-effect formula. Nude mice bearing human HCC xenografts underwent tumour resection (hepatectomy) 10 days post implantation, then received intraperitoneal administration of genistein or cisplatin alone or the combination of the two drugs. 33 days after surgery, recurrent tumours and pulmonary metastasis were evaluated individually. MMP-2 level in recurrent tumours was detected by immunohistochemistry and real-time PCR; MMP-2 expression in HCCLM3 was detected by immunocytochemistry. Results: Genistein and cisplatin both suppressed the growth and proliferation of HCCLM3 cells. The two drugs exhibited synergistic effects even at relatively low concentrations. In vivo, mice in the combined genistein and cisplatin group had a smaller volume of liver recurrent tumors and fewer pulmonary metastatic foci compared with single drug treated groups. Cisplatin upregulated the expression of MMP-2 in both recurrent tumours and HCCLM3, while genistein abolished cisplatin-induced MMP-2 expression. Conclusions: Genistein reinforced the inhibitory effect of cisplatin on HCC cell proliferation and tumour recurrence and metastasis after curative hepatectomy in nude mice, possibly through mitigation of cisplatin-induced MMP-2 upregulation.
Objectives: Alcohol abuse is a public issue and one of the major causes of liver disease worldwide. This study was aimed at investigating the protective effect of Ganoderma lucidum pharmacopuncture (GLP) against hepatotoxicity induced by acute ethanol (EtOH) intoxication in rats. Methods: Sprague-Dawley (SD) rats were divided into 4 groups of 8 animals each: normal, control, normal saline pharmacopuncture (NP) and GLP groups. The control, NP and GLP groups received ethanol orally. The NP and the GLP groups were treated daily with injections of normal saline and Ganoderma lucidum extract, respectively. The control group received no treatment. The rats in all groups, except the normal group, were intoxicated for 6 hours by oral administration of EtOH (6 g/kg BW). The same volume of distilled water was administered to the rats in the normal group. Two local acupoints were used: Qimen (LR14) and Taechung (LR3). A histopathological analysis was performed, and the liver function and the activities of antioxidant enzymes were assessed. Results: GLP treatment reduced the histological changes due to acute liver injury induced by EtOH and significantly reduced the increase in the alanine aminotransferase (ALT) enzyme; however, it had an insignificant effect in reducing the increase in aspartate aminotransferase (AST) enzyme. It also significantly ameliorated the superoxide dismutase (SOD) and the catalase (CAT) activities. Conclusion: The present study suggests that GLP treatment is effective in protecting against ethanol-induced acute hepatic injury in SD rats by modulating the activities of ethanol-metabolizing enzymes and by attenuating oxidative stress.
This study aimed to compare a microparticle enzyme immunoassay (MEIA) with a liquid chromatography-tandem mass spectrometry (LC/MS/MS) technique for the measurement of tacrolimus concentrations in adult liver transplant recipients, to investigate how the assay choice influenced the population pharmacokinetics of tacrolimus and to identify patient characteristics that affected pharmacokinetic parameters in each assay. Tacrolimus concentrations from 29 liver (n=52 paired-samples) transplant recipients measured by both MEIA and LC/MS/MS were used to evaluate the performance of these methods in the clinical setting. Tacrolimus pharmacokinetics was studied independently using MEIA and LC/MS/MS data in 70 adult patients using a population approach performed with NONMEM. Patient characteristics which influenced pharmacokinetic parameters in each assay were compared. The relation between LC/MS/MS and MEIA measurements was best described by the regression equation MEIA=1.465*LC/MS/MS-1.336 (r=0.91). Multiple linear regression analysis showed significant inverse relationships between assay difference and hematocrit (Hct) (p<0.025) in liver graft recipients. In MEIA, the population estimate of tacrolimus CL/F and apparent volume of distribution (Vd/F) were found to be 10.1 L/h and 226 L, and in LC/MS/MS, 13 L/h and 305 L respectively. Neither patient's age, weight, gender, grafted hepatic weight, albumin concentration, nor markers of liver function influenced tacrolimus CL/F The final model of CL/F was found to be 10.1+(Hct/Hct mean)$^{12.0}$ in MEIA and 13+(1+Hct/578) in LC/MS/MS indicating that CL/F was influenced by hematocrit.
This study was undertaken to find out the effect of persimmon leaves on histopathological changes of cadmium toxicity in mice. Seventy two BALB/c mice of male were divided into a control group(A) and five experimental groups (B, C, D, E, F) : group A received tap water and basal diet, group B received tap water and diet supplemented with 3% persimmon leaves alone, group C received basal diet and 300 ppm cadmium, group D, E and F received basal diet supplemented with 1, 3% and 7% persimmon leaves and 300 ppm cadmium respectively. Cadmium dissolved in tap water was used, and the persimmon leaves were mixed with feed. All mice were dissected on the 84th day. Pathological changes in liver, kidney, cortical osseous tissue of femoral shaft, bone trabecular of femur, and epiphyseal cartilage plate of femur were observed. Group B showed no significant changes as the control group. But group C showed the unclearness of specific cells in liver, the loss of architecture and necrosis of hepatocyte, degeneration and necrosis of renal convoluted tubules, desquamation and vacuolization of the greater part of the renal tubular epithelium, marked thinning of the cortical osseous tissue in femoral shaft, reduction of cancellous bone volume and decreaswe of trabecular number, and marked thinning of epiphyseal cartilage plate in femur. On the other hand, persimmon leaves-treated group showed a little convalescent changes an maintained their normal architectures in liver, kidney, cortical osseous tissue of femoral shaft, bone trabecular of femur, and epiphyseal cartilage plate of femur.
This study was performed to estimate the clinical signs and biochemical para meters of indicator on acute hepatic injury induced by the administration of CCl$_{4}$ in rats. Minor behavioral changer brittleness of skin hair and decreased volume of water and food intake were observed in rats after 2 hours of $CCl_{4}$ administration compared to control group. Concentration of serum albumin has shown lower than that of control group. However concentration of total bilirubin has shown higher than that of control group. As times go onto serum LDH activity was significantly increased compared to control Broup. Serum CPK activity hasn't shown change compared to control group. Passive hemagglutination that of afetoprotein was shown negative reaction in all the treatment groups and control group.
This study was performed to estimate the clinical signs and changes of biochemical parameters in rats with hepatic injury induced by the administration of 2, 2'-azobis(2- amidinopropane)dihydrochloride (AAPH) . Minor behavioral change, brittleness of skin hair and decreased volume of water and feed intake were observed in ra% 2 hours after AAPH administration compared to control group. Concentration of serum albumin showed lower than that of control group. However, concentration of total bilirubin has shown higher than that of control group. As time goes on, . serum LDH activity increased significantly compared to control group, but senun CPK activity did not change compared to control group. Passive hemanglutination of $\alpha $-fetoprotein was negative in all the treaDent groups and control group.
The conventional delivery quality assurance (DQA) process for RapidArc (Varian Medical Systems, Palo Alto, USA), has the limitation that it measures and analyzes the dose in a phantom material and cannot analyze the dosimetric changes under the motional organ condition. In this study, a DQA method was designed to overcome the limitations of the conventional DQA process for internal target volume (ITV) based RapidArc. The dynamic DQA measurement device was designed with a moving phantom that can simulate variable target motions. The dose distribution in the real volume of the target and organ-at-risk (OAR)s were reconstructed using 3DVH with the ArcCHECK (SunNuclear, Melbourne, USA) measurement data under the dynamic condition. A total of 10 ITV-based RapidArc plans for liver-cancer patients were analyzed with the designed dynamic DQA process. The average pass rate of gamma evaluation was $81.55{\pm}9.48%$ when the DQA dose was measured in the respiratory moving condition of the patient. Appropriate method was applied to correct the effect of moving phantom structures in the dose calculation, and DVH data of the real volume of target and OARs were created with the recalculated dose by the 3DVH program. We confirmed the valid dose coverage of a real target volume in the ITV-based RapidArc. The variable difference of the DVH of the OARs showed that dose variation can occur differently according to the location, shape, size and motion range of the target. The DQA process devised in this study can effectively evaluate the DVH of the real volume of the target and OARs in a respiratory moving condition in addition to the simple verification of the accuracy of the treatment machine. This can be helpful to predict the prognosis of treatment by the accurate dose analysis in the real target and OARs.
Kim, Heejin;Park, Seungwoo;Jung, Haijo;Kim, Mi-Sook;Yoo, Hyung Jun;Ji, Young Hoon;Yi, Chul-Young;Kim, Kum Bae
Progress in Medical Physics
/
v.24
no.2
/
pp.99-107
/
2013
The surgical resection was occurred mainly in liver metastasis before the development of radiation therapy techniques. Recently, Radiation therapy is increased gradually due to the development of radiation dose delivery techniques. 18F-FDG PET image showed better sensitivity and specificity in liver metastasis detection. This image modality is important in the radiation treatment with planning CT for tumor delineation. In this study, we applied automatic image segmentation methods on PET image of liver metastasis and examined the impact of image factors on these methods. We selected the patients who were received the radiation therapy and 18F-FDG PET/CT in Korea Cancer Center Hospital from 2009 to 2012. Then, three kinds of image segmentation methods had been applied; The relative threshold method, the Gradient method and the region growing method. Based on these results, we performed statistical analysis in two directions. 1. comparison of GTV and image segmentation results. 2. performance of regression analysis for relation between image factor affecting image segmentation techniques. The mean volume of GTV was $60.9{\pm}65.9$ cc and the $GTV_{40%}$ was $22.43{\pm}35.27$ cc, and the $GTV_{50%}$ was $10.11{\pm}17.92$ cc, the $GTV_{RG}$ was $32.89{\pm}36.8$4 cc, the $GTV_{GD}$ was $30.34{\pm}35.77$ cc, respectively. The most similar segmentation method with the GTV result was the region growing method. For the quantitative analysis of the image factors which influenced on the region growing method, we used the standardized coefficient ${\beta}$, factors affecting the region growing method show GTV, $TumorSUV_{MAX/MIN}$, $SUV_{max}$, TBR in order. The result of the region growing (automatic segmentation) method showed the most similar result with the CT based GTV and the region growing method was affected by image factors. If we define the tumor volume by the auto image segmentation method which reflect the PET image parameters, more accurate and consistent tumor contouring can be done. And we can irradiate the optimized radiation dose to the cancer, ultimately.
Comparison of the dose aspect that radiation therapy treatments using IMRT, tomotherapy, mArc (modulated arc therapy). The experimental subject is non-small cell lung cancer patient. The prescription dose is 58.0 Gy to the volume of PTV(planning target volume). and spinal cord, esophagus, and liver organ is the normal organ(OAR, organ at risk). Average PTV value is 57.60 Gy in mArc and 61.04 Gy in tomotherapy and 58.95 Gy in IMRT. The average dose of the Esophagus is 2.84 Gy in m-Arc, 5.14 Gy in tomotherapy, 1.84 Gy in IMRT. The average dose of the Liver is 19.44 Gy in m-Arc, 12.22 Gy in tomotherapy, 21.97 Gy in IMRT. The average dose of the Spinal cord is 5.72 Gy in m-Arc, 7.08 Gy in tomotherapy, 6.15 Gy in IMRT. Results of this study is no significant difference between mArc and tomotherapy and Linac based IMRT in dose study and also, mArc's dose coverage and dose volume histogram is better than IMRT and tomotherapy. but, This study is limited to a disease of cancer. in addition, fewer number of groups. The wide range the more research can be developed patient-specific treatment techniques and be applied to the patients
Kim, Song Yeon;Hwang, Tae Sung;An, Soyon;Hwang, Gunha;Go, Woohyun;Lee, Jong Bong;Lee, Hee Chun
Journal of Veterinary Clinics
/
v.38
no.3
/
pp.135-142
/
2021
The aim of this study was to evaluate the contrast effect if a saline flush following low-volume contrast medium bolus improves vascular and parenchymal enhancement using a saphenous vein in abdominal CT for small animals. Six clinically healthy beagle dogs underwent abdominal contrast-enhanced CT. They were divided into nine groups (each group, n = 6), according to the volume of contrast medium 1, 2, and 3 mL/kg, and volume of the saline solution 0, 5, and 10 mL. Dynamic CT scanning was performed at the hepatic hilum level. The maximum contrast enhancement, time to maximum enhancement, and time to equilibrium phase were calculated from the time attenuation curves. Mean attenuation values for all groups were measured in the aorta, portal vein, and liver. After contrast enhancement, grading of image quality regarding surrounding artifacts and evaluation of the hepatic hilum structures was performed. For comparison of the effect of the contrast material and saline solution doses, differences in mean attenuation values between the contrast medium 2 mL/kg without saline flush group and the remaining groups, and between contrast medium 3 mL/kg without saline flush group and the remaining groups, were analyzed for statistical significance. There were no significant differences between with and without saline flushing at the same contrast medium dose groups. There were no significant differences in peak values between the 3 mL/kg dose of contrast medium alone and the 2 mL/kg dose of contrast medium with saline solution flush. However, there was a significant difference in peak values between the 3 mL/kg dose of the contrast medium without the saline flush group and the 2 mL/kg dose of the contrast medium alone group. Grades of the artifacts were not significantly different in the saline flush regardless of the dose of the contrast medium. Using 2 mL/kg of contrast medium with saline solution flush resulted in similar liver parenchyma attenuation, compared with using 3 mL/kg of contrast medium without saline solution flush. In CT evaluation of hepatic parenchymal diseases, using 2 mL/kg of contrast medium with saline solution flush may yield decreased risk of contrast nephropathy and cost-saving.
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