scholarly journals Therapeutic response monitoring after targeted therapy in an orthotopic rat model of hepatocellular carcinoma using contrast-enhanced ultrasound: Focusing on inter-scanner, and inter-operator reproducibility

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0244304
Author(s):  
Hwaseong Ryu ◽  
Jung Hoon Kim ◽  
Seunghyun Lee ◽  
Joon Koo Han

Purpose To assess therapeutic response monitoring after targeted therapy in an orthotopic rat model of hepatocellular carcinoma (HCC) using CEUS with focusing on inter-scanner and inter-operator reproducibility. Materials and methods For reproducibility, CEUS was performed using two different US scanners by two operators in sixteen rat models of HCC. Using perfusion analysis software (VueBox ®), eleven parameters were collected, and intra-class correlation coefficient (ICC) was used to analyze reproducibility. Then seventeen rat models of HCC were divided into treatment group (n = 8, 30 mg/kg/day sorafenib for five days) and control group (n = 9). CEUS was performed at baseline and 14 days after first treatment, and changes of perfusion parameters were analyzed. Results In treatment group, CEUS perfusion parameters showed a significant change. The peak enhancement (PE, 2.50 x103±1.68 x103 vs 5.55x102±4.65x102, p = 0.010) and wash-in and wash out AUC (WiWoAUC, 1.07x105±6.48 x104 vs 2.65x104±2.25x104, p = 0.009) had significantly decreased two weeks after treatment. On the contrary, control group did not show a significant change, including PE (1.15 x103±7.53x102 vs 9.43x102± 7.81 x102, p = 0.632) and WiWoAUC (5.09 x104±3.25x104 vs 5.92 x104±3.20x104, p = 0.646). For reproducibility, the various degrees of inter-scanner reproducibility were from poor to good (ICC: <0.01–0.63). However, inter-operator reproducibility of important perfusion parameters, including WiAUC, WoAUC, and WiWoAUC, ranged from fair to excellent (ICC: 0.59–0.93) in a different scanner. Conclusion Our results suggest that CEUS is useful for assessment of the treatment response after targeted therapy and with fair to excellent inter-operator reproducibility.

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 94-94
Author(s):  
Hyoeun Yoo ◽  
Hyun-Sook Kim ◽  
Hyunjin Kim ◽  
Songhee Ahn ◽  
Xiangqin Zhou

Abstract Objectives Sprout of evening primrose (Oenothera laciniata, OL), Field horsetail (Equisetum arvense L., EAL), Tree of heaven (Ailanthus altissima, AA) leaves are all reported to be rich of flavonoids. This study was performed to determine the antioxidative effects of Sprout of evening primrose (Oenothera laciniata), Field horsetail (Equisetum arvense L.), Tree of heaven (Ailanthus altissima) leaves ethanol extracts in d-galactose induced aging rat model. Methods After 3weeks of adaptation period, 12-week-old SD rats were randomly divided into six groups (n = 5 each): Control group (C), D-galactose induced aging group (G), D-galactose injection with tomato treatment positive control group (PC), D-galactose injection with OL treatment group (O), D-galactose injection with EAL treatment group (E), D-galactose injection with AA treatment group (A). All groups except C group were intraperitoneally injected with D-galactose for 12 weeks and C group was treated with saline as a substitute. Results After 8 weeks of oral treatment period, there was no significant difference in body weight among six groups. Serum malondialdehyde (MDA) concentration levels increased significantly in G group compared to C group (P &lt; 0.05). Serum advanced glycation end (AGE) concentration levels decreased significantly in O group and A group compared to G group (P &lt; 0.05). Liver MDA level decreased significantly in O, E, A groups compared to G group (P &lt; 0.05). Conclusions Sprout of evening primrose (Oenothera laciniata, OL), Tree of heaven (Ailanthus altissima, AA) extract consumption can ameliorate antioxidative activities by suppressing oxidative stress in d-galactose induced aging rat model. Further research is under progress to clarify the mechanism of antioxidative effects. Funding Sources This study was partly funded and cooperated by Ministry of Commerce Industry and Energy.


2019 ◽  
Vol 2019 ◽  
pp. 1-6
Author(s):  
Jing-Hao Zhang ◽  
Chao Zheng ◽  
Xiao-Jun Zhu ◽  
Xin Zhang ◽  
Zhi-Jun Hou ◽  
...  

Objective. To ascertain the efficacy and safety of Ganji Formulation (GF) for patients with Hepatocellular carcinoma (HCC) who had undergone surgery. Materials and Methods. A total of 262 HCC patients who had undergone liver resection, local ablation, or transcatheter arterial chemoembolization (TACE) were divided randomly into the treatment group and control group. The former was treated with GF and the later with placebo, both for 6 months. The primary endpoint was overall survival (OS). Second endpoints were disease-free survival (DFS) or time to disease progression (TTP). Results. OS of the treatment group was significantly longer than that of the control group (P < 0.05). Subgroup analysis showed that, for patients who received TACE, the TTP was significantly longer in the treatment group than in the control group (P < 0.05). However, for patients who underwent liver resection or local ablation, there was no significant difference in DFS between the two groups (P > 0.05). Conclusion. GF could improve postoperative cumulative survival and prolong the TTP. This clinical trial number is registered with ChiCTR-IOR-15007349.


2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 408-408
Author(s):  
Mingsheng Huang ◽  
Qu Lin ◽  
HaoFan Wang ◽  
Long Wang ◽  
Mingjun Bai ◽  
...  

408 Background: The aim of this study is to investigate the survival benefit of transarterial chemoembolization (TACE) plus Iodine-125 seed implantation on Hepatitis B-related hepatocellular carcinoma (HB-HCC) patients complicated with PVTT and the underlying prognostic factors. Methods: A retrospective matched cohort study was done on unresectable HB-HCC patients with PVTT at our hospitals between January,2011 and June, 2014. The treatment group enrolled 70patients receiving TACE plus Iodine-125 seed implantation. The control group included 140 case-matched HB-HCC patients receiving TACE. The factors that might affect the overall survival (OS) were examined. Results: There was no significant difference in the baseline demographic characteristics between the two groups (p>0.05). Median survival time of the two groups was 11.0months and 7.5 months, respectively (P<0.001). The OS at 6, 12, 24, and 36 months was 85% vs 55%, 50% vs 25%, 14.5% vs 9%, and 14.5% vs 5% in the treatment group and control group, respectively (all P<0.001). The OS rate for type I+II PVTT patients, type III PVTT patients, patients complicated with arterial-portal-shunt (APS) or patients with mass/nodules in the treatment group was significantly higher than that in the control group (P=0.006, P<0.001, P<0.001,and P<0.001, respectively). Multivariate analysis showed that type III PVTT [Hazard ratio (HR)=0.274; 95% confidence interval (CI): 0.187~0.400; P<0.001], ECOG performance status 1~2 (HR=0.647; 95% CI: 0.428~0.979; P=0.039), diffusely infiltrating tumor subtype (HR=0.596; 95% CI: 0.417~0.852; P=0.005), and the presence of APS (HR=2.387; 95%CI: 1.594~3.574; P<0.001) were independent predictors of poor prognosis. Treatment modality of TACE plus Iodine-125 seed implantation (HR=0.291; 95% CI: 0.185~0.456; P<0.001) was independently associated with better survival. Conclusions: TACE plus Iodine-125 seed implantation can improve OS of unresectable HB-HCC patients with PVTT. Treatment modality, ECOG, PVTT type, presence of APS, and subtype of tumor were independent factors for predicting prognosis.


2020 ◽  
Vol 31 (1) ◽  
pp. 49
Author(s):  
Festi Artika Sari ◽  
Willy Sandhika ◽  
Tri Hartini Yuliawati

<p class="ISIABSTRAKINGGRIS">Gastritis is an inflammation of the gastric mucosa. Tulsi leaf extract has phenol, flavonoid and saponin compounds which are potential as antioxidant and increase defensive factors in the gastric. The purpose of this research was to find out the effect of tulsi (Ocimum sanctum) leaf extract in polymorphonuclear (PMN) inflammatory cell infiltration in gastric of aspirin-induced gastritis rat model. This study was laboratory experimental research using post-test only control group design. Randomly, 27 male rats were divided into 3 groups, the first group was not induced by aspirin and extract as negative control, the second group was induced by aspirin of 600 mg/kgBW as positive control, and the third group was induced by aspirin of 600 mg/kgBW and was given Ocimum sanctum extract at a dose of 400 mg/kgBW as treatment group. Gastric of the rats were taken on 16th day for histopathology evaluation using hematoxylin and eosin (HE) staining. Evaluation was done by calculating the PMN inflammatory cell infiltration in mucosal and submucosal layer. The results of the average number of PMN inflammatory cell in the gastric tissue of the treatment group showed a significant decrease compared to the positive and negative control groups with P-value &lt;0.05. This study proved that Ocimum sanctum leaf extract administration with the dose of 400 mg/kgBW can decrease gastritis inflammation by reducing PMN inflammatory cell in gastric of aspirin-induced gastritis rat model.</p>


2022 ◽  
Vol 71 (6) ◽  
pp. 2189-93
Author(s):  
Noaman Ishaq ◽  
Shabana Ali ◽  
Muhammad Waqar Aslam Khan ◽  
Kulsoom Farhat ◽  
Nausheen Ata ◽  
...  

Objective: To evaluate the chondroprotective effects of hyaluronic acid in a rat model of osteoarthritis. Study Design: Laboratory based experimental study. Place and Duration of Study: Department of Pharmacology, Army Medical College, Rawalpindi, in alliance with National Institute of health, Islamabad and Department of Pathology, Army Medical College Rawalpindi, from Apr to Jun 2019. Methodology: Sixteen (16) rats of Sprague Dawley breed were procured in this study. Osteoarthritis was induced in right knee joint of rats by surgical resection of medial meniscus and anterior cruciate ligament. They were allocated into two (02) groups with eight (08) rats in both groups. Group-I was control group that was treated with 0.2 ml intra articular saline once weekly for four weeks. While group-II was treatment group that was intra particularly administered with 0.2ml hyaluronic acid once weekly for four weeks. One week after the last dosage, gait pattern of the animals was scored. Then animals were sacrificed and a part of proximal tibia was obtained for histopathologic analysis. Results: Mean gait score of control group and treatment group was 3.25 ± 0.707 and 1.00 ± 0.756 respectively with a statistically significant p-value of <0.001, while mean histopathological Modified Mankin score of control and treatment group was 11.5 ± 1.195 and 5.50 ± 1.195 respectively with a significant p-value of <0.001. Conclusion: Intra articular viscosupplementation of hyaluronic acid in rat model of osteoarthritis resulted in improved gait pattern and histopathology.


2019 ◽  
Vol 52 (2) ◽  
pp. 61
Author(s):  
H. Hendrawati ◽  
Hanindya Noor Agustha ◽  
Rezmelia Sari

Background: Repair of bone damage represents a fundamental issue in the treatment of periodontitis. The important indicator employed to monitor the bone damage repair process is the number of osteoblast cells. Achatina Fulica snail mucin (SM) contains glycosaminoglycans which have the potential to increase their number. However, the use of SM in dentistry remains limited. Purpose: To determine and prove the effect of SM gel in increasing the number of osteoblasts in rat models suffering from periodontitis. Methods: This study used 36 rat models divided into three groups, namely; a treatment group (T: 20% snail mucin gel, n = 12), a positive-control group (P: hyaluronic acid gel, n = 12) and a negative-control group (N: CMC-Na gel, n = 12). 0.2 ml of all material was applied to a pocket by means of a tuberculin syringe once a day for 14 days. Histologic observations using Haematoxylin-Eosin staining were carried out on days 3, 5, 7 and 14. Data was analyzed by two-way ANOVA followed by a post-hoc LSD. Results: A significant difference existed between the number of osteoblasts in the test groups. The highest number of osteoblasts observed was consistently that in the treatment group. Conclusion: The application of 20% snail mucin gel was effective in enhancing the number of osteoblasts in rats suffering from periodontitis.


2021 ◽  
Vol 5 (5) ◽  
pp. 78-84
Author(s):  
Yu Cai ◽  
Chang Tian ◽  
Wujun Li ◽  
Pu Yan

Objective: To investigate the effect of sorafenib combined with interferon-lambda 3 on the growth of liver cancer transplanted into nude mice. Methods: Female nude mice of 4-5 weeks of age that passed quarantine were selected and fed for 1-2 weeks before experimental operation. The cell suspension of human hepatoma cell line SMMC-7721 was inoculated into the right cervical axillary fossa with a syringe. The tumor-bearing mice were randomly divided into a control group and an experimental group. The control group received normal saline whereas the experimental group was further divided into three other groups: IFN-lambda 3 treatment group, sorafenib treatment group, and IFN-lambda 3 combined with sorafenib treatment group. The situation of nude mice was analyzed. At the end of the experiment, the volume of allogeneic transplanted tumor was measured, and the morphology of tumor cells, the expression of proliferating protein Ki-67, as well as the number of apoptotic cells were observed by hematoxylin and eosin (H&E) staining, immunohistochemistry (IHC), and TUNEL staining. Results: The tumor cell volume of the IFN-lambda 3 treatment group, sorafenib treatment group, and IFN-lambda 3 combined with sorafenib treatment group decreased, which was statistically significant compared with the control group (p < 0.05). The increment rate of proliferating protein Ki-67 in the transplanted tumor tissue of the three drug groups was significantly lower than that of the control group (p < 0.05). IFN-lambda 3 combined with sorafenib had the greatest effect on the expression level of Ki-67 protein. Compared with the control group, the expression rate was significantly lower (p < 0.05). In terms of cell apoptosis, IFN-lambda 3 and/or sorafenib, as well as the combination of the two, showed statistically significant differences compared with the control group (p < 0.05). The rate of cell apoptosis was the highest in the IFN-lambda 3 combined with sorafenib group. Conclusion: IFN-lambda 3 combined with sorafenib can inhibit the growth and proliferation of human hepatocellular carcinoma cells in nude mice and promote the apoptosis of hepatocellular carcinoma cells, which proves that IFN-lambda 3 combined with sorafenib can treat hepatocellular carcinoma in vivo.


2020 ◽  
Vol 21 (4) ◽  
pp. 588-595
Author(s):  
Ayu Miftahul Khasanah ◽  
Niswah Nurul Fahma ◽  
Tri Wahyu Pangestiningsih

Red nucleus plays a role in motoric control, so that disturbanced of neurons in this nucleus could be affected on motor impairment. Previous study reported that paraquat (PQ) could induced Parkinson disease, a neurodegeneratif disease that affected subtantia nigra pars compactca and clinically characterized by motoric disorders. Apoptosis is a programed cell death that physiologically normal for the body, but in large quantities will cause progresive cell death. This study aimed to observed apoptosis in rats RN neurons following by PQ injection. Ten male Wistar rats with the aged of 3 month, devided into two groups of five. Control group was given aquadest and treatment group was given PQ, injected intraperitoneally, dosage 7 mg/kg BW, twice a week for three weeks. At day 24th all rats were anesthetized using ketamin dosage 40 mg/kg BW and xylazine dosage 5 mg/kg BW, perfused intracardially using 4% paraformaldehyde and mesencephalons were collected. Mesencephalons were processed for histological preparations using the paraffin method and cut stereologically in coronal section, in 4 ?m thickness. Immunohistochemistry staining was done using caspase 3 antibody as a marker of apoptosis. Data were analyzed descriptively and quantitatively. The results in both groups showed RN neurons were large size and stelat or fusiform in shape. The percentage of apoptotic neurons in the RN of treatment group was significantly increased (80,4%±13,8%) compared to the control group (26,6%±18,32%) (P<0.01). In conclusion, following PQ exposure there is a significant increased of apoptosis neurons number in the RN of rat model of Parkinson disease.


2018 ◽  
Vol 46 (6) ◽  
pp. 2325-2334 ◽  
Author(s):  
Chun Gui ◽  
Zhi-yu  Zeng ◽  
Qi Chen ◽  
Ya-wei Luo ◽  
Lang Li ◽  
...  

Background/Aims: Microvascular insufficiency takes a critical role in the development of diabetic cardiomyopathy (DCM). So this study was designed to investigate the effects of Neuregulin-1 (NRG-1) treatment on myocardial angiogenesis and the changes of VEGF/Flk1 and Ang-1/Tie-2 signaling in the rat model of DCM. Methods: Diabetic rats were induced by a single intraperitoneal injection of Streptozotocin. 12 weeks after the diabetes induction, the rats with NRG-1 treatment were treated with tail vein injection of NRG-1 at the dose of 10µg/kg/d for consecutive 10 days. Cardiac function was assessed using catheter MPA cardiac function analysis system. Myocardial blood flow (MBF) was assessed with stable-isotope labeled microspheres. Capillary density was measured by CD31 immunohistochemistry. The protein expression and receptors phosphorylation were assessed using western blot. Results: Left ventricular function, capillary density and MBF were significantly reduced in DCM group when compared with those in the control group (P< 0.01, P< 0.01 and P< 0.05 respectively). Left ventricular function and capillary density were significantly increased in NRG-1 treatment group when compared with those in the DCM group (P< 0.05 and P< 0.05 respectively). The expression of VEGF and Ang-1 and the phosphorylation of Flk1 and Tie-1 were significantly decreased in DCM group as compared with those in the control group. However, those in the NRG-1 treatment group were significantly increased as compared with those in the DCM group. In vitro, NRG-1 treatment increased significantly the expression of VEGF and Ang-1 in human coronary artery smooth muscle cells. Conclusions: NRG-1 can increase the myocardial angiogenesis of DCM, probably via the direct effects of NRG-1 and via the increasing expression of VEGF and Ang-1. These findings may contribute to developing a novel approach to reverse the impaired angiogenic responses in diabetes or coronary artery disease.


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