Objective: Bufonis Venenum is the traditional Korean medicine Chan Su, which is obtained from the skin and parotid venom gland of the toads. It has been used for myocardial diseases, inflammation diseases, pain relief, cancer and others. The main components of BV are cinobufotoxin, cinobufalin, bufalin and others. Of these, bufalin, the major active ingredient of BV, has been reported to induce apoptosis and to possess anti-tumor effects. There was no report of anti-tumor screening of BV on hepatic cancer and which signaling pathway can be involved. In order to examine the effect of BV on hepatic cancer and the related signaling pathway with BV-induced apoptosis, human Hep G2 cells were used. Methods: Analysis of apoptosis was confirmed by MTT assay. BV decreased cell viability in a dose and duration dependent manner. To observe which signaling molecules will be activated by BV, phosphorylation of MAPK (p38, ERK, JNK), caspase 8 and caspase 9 were examined by Western blot analysis. Results: The phosphorylation levels of p38 started to increase at 5 min after addition of 5 ${\mu}g$/ml of BV and sustained to increase until 48 hours. The phosphorylation levels of other MAPK (ERK and JNK), caspase 8 and caspase 9 increased in a time-dependent manner. These imply that BV may activate different signaling pathways, MAPK, caspase 8 and caspase 9. These results propose that BV may induce apoptosis on Hep G2 cells through the activation of MAPK, caspase 8 and caspase 9.
Treatment for the brain tumors consist of surgery, chemotherapy, and a variety of methods of irradiation. Therapy is aimed to destroy the tumor, but necrosis and edema occur concurrently. Conventional structural imaging techniques such as CT or MRI are unable to reliably distinguish persistent and recurrent tumor from necrosis or edema. T1-201 has been shown to be useful in the evaluation of the myocardial viability by comparing the early uptake and redistribution image. The aim of this study is to evaluate the clinical usefulness of the early uptake and delayed washout images of the T1-201 brain SPECT in the brain tumors. In the pathologically diagnosed various brain tumor patients, brain SPECT was done with rotating gamma camera 15 minutes and 3 hours after T1-201 injection, and the T1-201 uptake in the tumor was compared with the skull and scalp activity. In the glioblastoma multiforme, meningioma and metastatic tumor, the T1-201 uptake was higher than low grade glioma in both 15 minute and 3 hour images (p<0.02). In the low grade glioma,3 hour T1-201 uptake was significantly lower than 15 minute uptake (p<0.05) but in the glioblastoma, meningioma and metastatic tumor there was no significant difference. There was no significant difference in the T1-201 uptake among the glioblastoma, meningioma and metastatic tumors. In one matastatic tumor, T1-201 uptake was decreased after radiation therapy. T1-201 brain SPECT could distinguish the benign and malignancy, and seems to be useful in the follow-up after treatment. But one of the early or delayed SPECT seems not to be necessary for these purposes.
Du, Jian;Yang, Si-Tong;Liu, Jia;Zhang, Ke-Xin;Leng, Ji-Yan
Molecules and Cells
/
v.42
no.5
/
pp.397-405
/
2019
The regulatory role of long noncoding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) in both cancerous and noncancerous cells have been widely reported. This study aimed to evaluate the role of lncRNA GAS5 in heart failure caused by myocardial infarction. We reported that silence of lncRNA GAS5 attenuated hypoxia-triggered cell death, as cell viability was increased and apoptosis rate was decreased. This phenomenon was coupled with the down-regulated expression of p53, Bax and cleaved caspase-3, as well as the up-regulated expression of CyclinD1, CDK4 and Bcl-2. At the meantime, the expression of four heart failure-related miR-NAs was altered when lncRNA GAS5 was silenced (miR-21 and miR-142-5p were up-regulated; miR-30b and miR-93 were down-regulated). RNA immunoprecipitation assay results showed that lncRNA GAS5 worked as a molecular sponge for miR-142-5p. More interestingly, the protective actions of lncRNA GAS5 silence on hypoxia-stimulated cells were attenuated by miR-142-5p suppression. Besides, TP53INP1 was a target gene for miR-142-5p. Silence of lncRNA GAS5 promoted the activation of PI3K/AKT and MEK/ERK signaling pathways in a miR-142-5p-dependent manner. Collectively, this study demonstrated that silence of lncRNA GAS5 protected H9c2 cells against hypoxia-induced injury possibly via sponging miR-142-5p, functionally releasing TP53INP1 mRNA transcripts that are normally targeted by miR-142-5p.
Cherry Kim;Chul Hwan Park;Do Yeon Kim;Jaehyung Cha;Bae Young Lee;Chan Ho Park;Eun-Ju Kang;Hyun Jung Koo;Kakuya Kitagawa;Min Jae Cha;Rungroj Krittayaphong;Sang Il Choi;Sanjaya Viswamitra;Sung Min Ko;Sung Mok Kim;Sung Ho Hwang;Nguyen Ngoc Trang;Whal Lee;Young Jin Kim;Jongmin Lee;Dong Hyun Yang
Korean Journal of Radiology
/
v.23
no.3
/
pp.298-307
/
2022
Objective: This study aimed to evaluate the effect of implementing the consensus statement from the Asian Society of Cardiovascular Imaging-Practical Tutorial 2020 (ASCI-PT 2020) on the reliability of cardiac MR with late gadolinium enhancement (CMR-LGE) myocardial viability scoring between observers in the context of ischemic cardiomyopathy. Materials and Methods: A total of 17 cardiovascular imaging experts from five different countries evaluated CMR obtained in 26 patients (male:female, 23:3; median age [interquartile range], 55.5 years [50-61.8]) with ischemic cardiomyopathy. For LGE scoring, based on the 17 segments, the extent of LGE in each segment was graded using a five-point scoring system ranging from 0 to 4 before and after exposure according to the consensus statement. All scoring was performed via web-based review. Scores for slices, vascular territories, and total scores were obtained as the sum of the relevant segmental scores. Interobserver reliability for segment scores was assessed using Fleiss' kappa, while the intraclass correlation coefficient (ICC) was used for slice score, vascular territory score, and total score. Inter-observer agreement was assessed using the limits of agreement from the mean (LoA). Results: Interobserver reliability (Fleiss' kappa) in each segment ranged 0.242-0.662 before the consensus and increased to 0.301-0.774 after the consensus. The interobserver reliability (ICC) for each slice, each vascular territory, and total score increased after the consensus (slice, 0.728-0.805 and 0.849-0.884; vascular territory, 0.756-0.902 and 0.852-0.941; total score, 0.847 and 0.913, before and after implementing the consensus statement, respectively. Interobserver agreement in scoring also improved with the implementation of the consensus for all slices, vascular territories, and total score. The LoA for the total score narrowed from ± 10.36 points to ± 7.12 points. Conclusion: The interobserver reliability and agreement for CMR-LGE scoring for ischemic cardiomyopathy improved when following guidance from the ASCI-PT 2020 consensus statement.
Kim, Sung Hwan;Ryu, Jae Kwang;Yoon, Soon Sang;Kim, Eun Hye
The Korean Journal of Nuclear Medicine Technology
/
v.17
no.1
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pp.18-24
/
2013
Purpose: Myocardial perfusion SPECT using $^{201}Tl$ is an important method for viability of left ventricle and quantitative evaluation of cardiac function and now various reconstruction methods are used to improve the image quality. But in case of small sized heart, you should always be careful because of the Partial Volume Effect which may cause errors of quantitative indices at the reconstruction step. So, In this study, we compared those quantitative indices of left ventricle according to the reconstruction method of myocardial perfusion SPECT with the Echocardiography and verified the degree of the differences between them. Materials and Methods: Based on ESV 30 mL of Echocardiography, we divided 278 patients (male;98, female;188, Mean age;$65.5{\pm}11.1$) who visited the Asan medical center from February to September, 2012 into two categories; below the criteria to small sized heart, otherwise, normal or large sized heart. Filtered and output each case, we applied the method of FBP and OSEM to each of them, and calculated EDV, ESV and LVEF, and we conducted statistical processing through Repeated Measures ANOVA with indices that measured in Echocardiography. Results: In case of men and women, there were no significant difference in EDV between FBP and OSEM (p=0.053, p=0.098), but in case of Echocardiography, there were meaningful differences (p<0.001). The change of ESV especially women in small sized heard, significant differences has occurred among FBP, OSEM and Echocardiography. Also, in LVEF, there were no difference in men and women who have normal sized heart among FBP, OSEM and Echocardiography (p=0.375, p=0.969), but the women with small sized heart have showed significant differences (p<0.001). Conclusion: The change in quantitative indices of left ventricle between Nuclear cardiology image reconstruction, no difference has occurred in the patients with normal sized heart but based on ESV, under 30 mL of small sized heart, especially in female, there were significant differences in FBP, OSEM and Echocardiography. We found out that overestimated LVEF caused by PVE can be reduced in average by applying OSEM to all kinds of gamma camera, which are used in analyzing the differences.
An animal experiment was designed for the evaluation of in vivo performance of the newly developed electrohydraulic type ventricular assist device and its influence on the left ventricular function during pal- satile left ventricular assist. Eight adult sheep were incorporated into the study and data were collected from seven sheep. Total as- sist time ranged from 69 minutes to 7 days. The performance of the device was satisfactory both in asyn- chr nous and synchronous mode within the range of given native heart rate. More than 4 liters of device output could be reached within the range of normal left atral pressure without development of negative pressure in the left atrium. Moderate to severe degree of hemolysis was noted as evidenced by significant increase of plasma free hemoglobin level after 3 days of left ventricular support along with the presence of the small amount of thrombi around the floating disc type polymer valve apparatus reflecting that further study and refinement of the device need to be done in regard of biocompatibility and thromboresistance. The hemodynamics showed increase in heart rate (p < 0.05), cardiac output and left ventricular minute work (p < 0.05) after placement of the device at the flow rate of 2.0∼2.5 Llmin. The left atrial pressure, left ventricular pressure and LV dpldt were decreased after the device placement(p < 0.05). The endocardial viability ratio and oxygen contents of the mixed ven us blood and coronary venous blood were all increased (p < 0.05) after the device placement suggesting effective unloading of the left ventricle was accomplished. The myocardial perfusion was thought improved in synchronous counterpulsation as suggested by sig- nificant increase in endocardial viability ratio and coronary venous blood oxygen content in synchronous assist mode comparing with asynchronous mode.
To assess contribution of T1-201 rest-24 hour delay redistribution in detection of viable myocardium, we studied the predictive value of this redistribution in 17 patients who peformed rest-24 hour delay perfusion SPECT before bypass surgery. Regional wall motion was compared with gated SPECT in 10 patients and echocardiography in 7 patients before and after bypass surgery. Rest and 24 hour delayed uptakes were scored from 0 (normal perfusion) to 3 (defect). In rest SPECT, 56 segments showed perfusion decrease. Thirty four segments(61%) improved after surgery and were defined as viable Nineteen(34%) segments had more uptake of T1-201 at 24 hour delay, and the other 37 segments did not. In 81%(25/31) of segments with mildly decreased perfusion, wall motion after bypass surgery improved, 57% (8/14) of segments with severely decreased perfusion improved, and 9%(1/11) of segments with defects improved. In 14 among 19 segments which had more T1-201 uptakes at 24 hour delay, wall motion was improved(positive predictive value of redistribution: 74%). 20 among 37 segments which had persistent decreases in rest-24 hour redistribution improved and 17 did not(negative predictive value: 46%). Segments having severe perfusion decrease or defects showed improved wall motion after surgery in 64%(7/11), if it had redistribution at delay. Segments with either mildly decreased uptake in resting or rest-delayed redistribution showed improved wall motion in 76%(32/42). Among the 14 segments which showed improvement in wall motion, 10 had partial reversibility in stress-rest images and the other 4 had persistent perfusion defects in stress-rest images. These 4 segments were found viable only with rest-24 hour delayed perfusion SPECT. We concluded that rest T1-201 uptake or redistribution at 24 hour delay should be referred as an evidence to warrant postoperative improvement of abnormal wall motion and we could predict myocardial viability with preoperative rest-24 hour delay perfusion SPECT in the segments with rest perfusion decreases.
Purpose: The performance of nitroglycerin-challenged Tc-99m-MIBI quantitative gated SPECT for the detection of viable myocardium was compared with rest/24-hour redistribution Tl-201 SPECT Materials and Methods: In 22 patients with coronary artery disease, rest Tl-20l/ dipyridamole stress Tc-99m-MIBI gated/24-hour redistribution Tl-201 SPECT were peformed, and gated SPECT was repeated on-site after sublingual administration of nitroglycerin (0.6 mg). Follow-up gated SPECT was done 3 months after coronary artery bypass graft surgery. For 20 segments per patient, perfusion at rest and 24-hour redistribution, and wall motion and thickening at baseline and nitroglycerin-challenged state were quantified. Quantitative viability markers were evaluated and compared;(1) rest thallium uptake, (2) thallium uptake on 24-hour redistribution SPECT, (3) systolic wall thickening at baseline, and (4) systolic wall thickening with nitroglycerin-challenge. Results: Among 100 revascularized dysfunctional segments, wall motion improved in 66 segments (66%) on follow-up gated myocardial SPECT after bypass surgery. On receiver operating characteristic (ROC) curve analysis, the sensitivity and specificity of rest and 24-hour delayed redistribution Tl-201 SPECT were 79%, 44% and 82%, 44%, respectively, at the optimal cutoff value of 50% of Tl-201 uptake. The sensitivity and specificity of systolic wall thickening at baseline and nitroglycerin-challenge were 49%, 50% and 64%, 65% at the optimal cutoff value of 15% of systolic wall thickening. Area under the ROC curve of nitroglycerin-challenged systolic wall thickening was significantly larger than that of baseline systolic wall thickening (p=0.004). Conclusion: Nitroglycerin-challenged quantitative gated Tc-99m-MIBI SPECT was a useful method for predicting functional recovery of dysfunctional myocardium.
Kim, Jae-Sung;Lee, Dong-Soo;Hong, Suk-Keun;Lee, Young-Tak;Kim, Yu-Kyeong;Kim, Youn-Jung;Moon, Keon-Sik;Won, Tae-Kyoung;Hwang, Hweung-Kon
The Korean Journal of Nuclear Medicine
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v.34
no.4
/
pp.276-284
/
2000
Purpose: We investigated the operative outcome after bypass surgery in patients selected using viability criteria on F-18 FDG PET. Materials and Methods: Rest-24hr delay redistribution imaging of Tl-201 SPECT and F-18 FDG PET were performed in 11 patients. Seven of these 11 patients (6 men, 1 woman) were evaluated to have viable myocardium by F-18 FDG PET. Changes in symptoms and left ventricular ejection fraction (LVEF) after operation were evaluated. Results: In seven of 11 patients, a significant amount of viable myocardium was found on F-18 FDG PET and Tl-201 SPECT. Severity of both chest pain and dyspnea improved markedly in all patients. Mean LVEF improved from 22% to 32%. Conclusion: F-18 FDG PET could be used to select the patients who will benefit from coronary artery bypass surgery.
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