scholarly journals Experimental Research on the Inhibitory Effect of IFN-Lambda 3 Combined with Sorafenib on the Growth of Liver Cancer Transplanted into Nude Mice

2021 ◽  
Vol 5 (5) ◽  
pp. 78-84
Author(s):  
Yu Cai ◽  
Chang Tian ◽  
Wujun Li ◽  
Pu Yan
Keyword(s):  
Hepatocellular Carcinoma ◽  
Treatment Group ◽  
Nude Mice ◽  
Carcinoma Cells ◽  
Control Group ◽  
Ki 67 ◽  
Sorafenib Treatment ◽  
Transplanted Tumor ◽  
Experimental Group ◽  
Ifn Lambda

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.

scholarly journals Cardamonin Exerts Antitumor Effect on Human Hepatocellular Carcinoma Xenografts in Athymic Nude Mice through Inhibiting NF-κβ Pathway

Biomedicines ◽  
2020 ◽  
Vol 8 (12) ◽  
pp. 586
Author(s):  
Nassrin Badroon ◽  
Nazia Abdul Majid ◽  
Fouad Al-Suede ◽  
Mansoureh Nazari V. ◽  
Nelli Giribabu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Docking ◽  
Nude Mice ◽  
Untreated Control ◽  
Human Hepatocellular Carcinoma ◽  
Control Group ◽  
Ki 67 ◽  
Athymic Nude Mice ◽  
Bax Protein

Cardamonin (CADMN) exerts an in vitro antiproliferative and apoptotic actions against human hepatocellular carcinoma cells (HepG2). This study aimed to investigate the in vivo anti-tumorigenic action of CADMN against human hepatocellular carcinoma xenografts in an athymic nude mice, as well as to study the molecular docking and safety profile of this compound. Acute toxicity study demonstrated that CADMN is safe and well-tolerated up to 2000 mg/kg in ICR mice. Oral administration of 50 mg/kg/day of CADMN in xenografted nude mice showed a significant suppression in tumor growth as compared to untreated control group without pronounced toxic signs. Immunohistochemistry assay showed downregulation of proliferative proteins such as PCNA and Ki-67 in treated groups as compared to untreated control. Additionally, immunofluorescence analysis showed a significant downregulation in anti-apoptotic Bcl-2 protein, whereas pre-apoptotic Bax protein was significantly upregulated in nude mice treated with 25 and 50 mg/kg CADMN as compared to untreated mice. The findings also exhibited down-regulation of NF-κB-p65, and Ikkβ proteins, indicating that CADMN deactivated NF-κB pathway. The molecular docking studies demonstrated that CADMN exhibits good docking performance and binding affinities with various apoptosis and proliferation targets in hepatocellular cancer cells. In conclusion, CADMN could be a potential anticancer candidate against hepatocellular carcinoma. Other pharmacokinetics and pharmacodynamics properties, however, need to be further investigated in depth.

scholarly journals Clinical Study of Acupotomy Trinity Lysis on Cervical Spondylotic Myelopathy with Liver and Kidney Deficiency Syndrome

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Jianyong Gao ◽  
Yi Zhao ◽  
Tinglan Sun ◽  
Weike Liu ◽  
Zhenguo Wang
Keyword(s):  
Treatment Group ◽  
Cervical Spondylotic Myelopathy ◽  
Deficiency Syndrome ◽  
Control Group ◽  
Therapeutic Effects ◽  
Kidney Deficiency ◽  
Significant Difference ◽  
Before And After ◽  
Liver And Kidney ◽  
Experimental Group

Objective: To compare the therapeutic effects of acupotomy trinity lysis and traditional acupotomy on cervical spondylotic myelopathy. Methods: A total of 205 patients with cervical spondylotic myelopathy of liver and kidney deficiency syndrome were randomly divided into the experimental group (105 cases) and the control group (100 cases). The experimental group was relaxed with acupotomy in three positions: Heaven (tian), Human (ren) and Earth (di). Traditional acupotomy was used to relax Ashi acupoints of the affected vertebra in the control group. One treatment was conducted in one week, and the duration of one course of treatment was three weeks. The VAS, JOA score and NDI index were observed after treatment.  Results: Before and after treatment, the total treatment efficiency of the treatment group was 95.23%, and that of the control group was 80.00%, there was significant difference between the two groups, P<0.05; Before operation, there was no significant difference in JOA score, NDI index score, and VAS score between the treatment group and the control group (P>0.05); there was no significant difference after 1 week (P>0.05), but there were significant differences between the two groups 2 weeks and 3 weeks after operation (P<0.05). Conclusion: Acupotomy trinity lysis is a safe, effective and economical treatment for cervical spondylotic myelopathy.

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
Keyword(s):  
Hepatocellular Carcinoma ◽  
Targeted Therapy ◽  
Treatment Group ◽  
Rat Model ◽  
Therapeutic Response ◽  
Response Monitoring ◽  
Control Group ◽  
Rat Models ◽  
Significant Change ◽  
Operator Reproducibility

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.

scholarly journals Ganji Formulation for Patients with Hepatocellular Carcinoma Who Have Undergone Surgery: A Multicenter, Randomized, Double-Blind, Controlled Trial

2019 ◽  
Vol 2019 ◽  
pp. 1-6
Author(s):  
Jing-Hao Zhang ◽  
Chao Zheng ◽  
Xiao-Jun Zhu ◽  
Xin Zhang ◽  
Zhi-Jun Hou ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Treatment Group ◽  
Liver Resection ◽  
Controlled Trial ◽  
Disease Free Survival ◽  
Control Group ◽  
Double Blind ◽  
Local Ablation ◽  
Significant Difference ◽  
And Control

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.

Survival benefit of TACE plus iodine-125 seed implantation in unresectable hepatitis b-related hepatocellular carcinoma with PVTT.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 408-408
Author(s):  
Mingsheng Huang ◽  
Qu Lin ◽  
HaoFan Wang ◽  
Long Wang ◽  
Mingjun Bai ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Treatment Group ◽  
Hepatitis B ◽  
Treatment Modality ◽  
Survival Benefit ◽  
Control Group ◽  
Type I ◽  
Seed Implantation ◽  
Type Iii ◽  
Iodine 125

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.

Sorafenib as an adjuvant therapy for hepatocellular carcinoma with microvascular invasion after radical resection: A prospective multicenter nonrandomized controlled study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16685-e16685
Author(s):  
Li Xu ◽  
Yuhao Tang ◽  
Hua Li ◽  
Jie Zhou ◽  
Zhongguo Zhou ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Survival Data ◽  
Radical Resection ◽  
Microvascular Invasion ◽  
Controlled Study ◽  
Cancer Center ◽  
Control Group ◽  
Open Label ◽  
Recurrence Rates ◽  
Sorafenib Treatment

e16685 Background: Hepatocellular carcinoma (HCC) with microvascular invasion (MVI) is established with poorer outcome and more frequent postoperative recurrence. Sorafenib is the first target drug that successfully prolongs the survival of advanced HCC, but it failed to prolong the survival of HCC after radical resection or ablation in the STORM study. After that, series studies revealed that sorafenib could improve the survival of HCC with MVI after surgery, while most studies with positive results were retrospective ones. Methods: A multicenter, prospective non-randomized, open-label study was performed in pts undergoing radical resection, postoperative pathology confirming HCC with MVI (BCLC A or B stage; T2 or part T3aN0M0). Pts in the treatment group (S group) started sorafenib within 4-6 postoperative weeks at the dose of 400mg per day at most 2 years, and the control group (C group) never received sorafenib. The primary endpoint is recurrence-free survival (RFS) rate at the 2nd postoperative year, and the secondary endpoints include postoperative median time to recurrence (TTR), 1-year postoperative RFS, pts’ overall survival (OS), and safety. This study was approved by Ethical Committee of Sun Yat-sen University Cancer Center, and registered at ClinicalTrials.gov with number NCT02867280. Results: Between 1 June 2015 and 31 August 2019, 154 eligible pts from 3 academic hospitals in China were enrolled (83 in C group and 53 in S group). Baseline demographics were balanced between the two groups. The 2-yr RFS rate was 56.1% in the S group vs. 55.7% in the C group, respectively ( P = 0.955), and the median RFS was 15.5 vs. 16.0 months ( P = 0.827).The recurrence rates at the 1st postoperative year were 38.6% vs. 34.0% ( P = 0.568), and the median TTR was the same as the RFS. There were 31 pts (54.4%) of the S group experienced treatment-related adverse events (AEs). The most common AE was hand-foot syndrome (HFS, 19/57, 10 pts ≥ grade-2). Other AEs included diarrhoea (15/57, 26.4%), alopecia (11/57, 19.3%), hypertension (5/57, 8.8%) and decreased platelet (3/57, 5.3%), and gastric ulcer with bleeding (1/57, 1.8%). Sorafenib was interrupted or discontinued in 7 pts due to AEs. Recruiting of this study was closed according to the results of the planned mid-term analysis, and all pts were followed on schedule to observe the other survival data. Conclusions: Postoperative sorafenib treatment with dose of 400mg once daily was well tolerated, but did not improve the RFS and TTR of Chinese HCC pts with MVI. Clinical trial information: NCT02867280 .

scholarly journals MiR-375 gene therapy attenuates drug resistance of hepatocellular carcinoma cells by inhibiting cell autophagy

2020 ◽  
Author(s):  
Dan Wang ◽  
Jingbo Yang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Drug Resistance ◽  
Western Blotting ◽  
Regulatory Mechanism ◽  
Negative Control ◽  
Carcinoma Cells ◽  
Luciferase Reporter ◽  
Sorafenib Treatment ◽  
Hcc Cells ◽  
Dual Luciferase Reporter Assay

Abstract Objective To probe into the regulatory mechanism of miR-375 in hepatocellular carcinoma (HCC) cells under sorafenib treatment. Methods Western blotting and qRT-PCR were applied to measure the expressions of miR-375 and SIRT5 in parental HCC cells (HepG2 and Huh7) and sorafenib-resistant HCC cells (HepG2/so and Huh7/so). HepG2/so cells were accordingly transfected with miR-375 mimic, miR-375 inhibitor, sh-SIRT5, pcDNA3.1-SIRT5 or negative control. Western blotting measured the expressions of p62, LC3I and LC3II in HCC cells. CCK-8 and flow cytometry assessed the survivability and apoptosis of HCC cells, respectively. Bioinformatics techniques and dual-luciferase reporter assay predicted and verified the targeting relationship between miR-375 and SIRT5. Results MiR-375 was under-expressed and SIRT5 was over-expressed in HCC cells. Autophagy inhibitor impaired the survival of HepG2/so cells transfected with miR-375 inhibitor. Autophagy activator enhanced the drug resistance of HepG2/so cells transfected with miR-375 mimic. MiR-375 suppressed the drug resistance of HepG2/so cells by inhibiting autophagy. SIRT5 enhanced the drug resistance of HepG2/so cells by promoting autophagy and it could be targeted by miR-375. Conclusion MiR-375 suppresses autophagy to attenuate the drug resistance of HCC cells by regulating SIRT5. The findings of this study may provide new therapeutic targets for treating hepatocellular carcinoma.

Partial hepatectomy against the background of superinvasive opisthorchiasis does not provoke carcinogenesis

2021 ◽  
Vol 22 (2) ◽  
pp. 29-35
Author(s):  
S. D. Lazarev ◽  
◽  
E. D. Khadieva ◽  
V. G. Bychkov ◽  
L. V. Vikhareva ◽  
...  
Keyword(s):  
Partial Hepatectomy ◽  
Microscopic Analysis ◽  
Normal Structure ◽  
Regenerative Process ◽  
Middle Lobe ◽  
Control Group ◽  
Electron Microscopic ◽  
Ki 67 ◽  
Research Goal ◽  
Experimental Group

Research goal: identification of the risk of oncogenesis in the liver under the influence of 2 promoter factors – partial hepatectomy (PHE) performed against the background of superinvasive opisthorchiasis (SO) in Syrian hamsters. Material and methods. SO was modeled by infecting animals (n = 86) with 50 metacercariae of O. felineus. Superinvasions (50 metacercariae) were repeated 6 and 16 days after primary infection. PHE – removal of the middle lobe of the liver – 17.3-17.7% of the organ weight was performed according to the method of G. M. Higgins, K. M. Andersson 16 days after the last superinvasion. The quantitative assessment of the regenerative process after PHE was determined by the coefficients of regeneration completeness (%) by the formula Кпрп = (М1 – М2) / М3 × 100. The histological specimens were stained with hematoxylin and eosin and by the methods of Van Gieson, Slinchenko, Samsonov, Kupriyanov. IHC–reactions were carried out with antibodies to Ki–67, CD31, CD34, CD117, Oct 4, and α–fetoprotein. Electron microscopic analysis was performed on a “JEM – 100CX” microscope (JEOL, Ltd., Japan). The quantitative characteristics were processed using the statistical software Microsoft Excel (2019) and the Statistica package (version 12.6). Results. Analysis of the obtained data indicates that by the 16th day after PHE, 3 zones have formed in the liver: zone A – the stump, zone B – is adjacent to the wound zone A, zone C – is adjacent to zone B. By the 16th day after PHE, expressed proliferation processes of the CD31, CD34, Oct 4, CD117–positive cells and differentiation into endothelial cells, cholangiocytes, hepatocytes with the formation of vessels are noted. At a later date of the experiment, hepatocyte fields with the presence of α–fetoprotein in the cytoplasm, cholangiocellular tubules were formed; at a later date (23 days), ducts lined with a cylindrical epithelium of normal structure were identified. The epithelial lining of the preexisting ducts is multi–row by the end of the experiment; no tumors were found in the liver in the experimental group. An increase in liver mass was noted in the control group (SO) by 8.2%, in the experimental group – 24.7%. Conclusion. The liver with partial hepatectomy against the background of superinvasive opisthorchiasis is an organ with permanent proliferation of CCD and HCD cells, hyperregeneration and a significant increase in mass. In the presence of 2 promoters without initiators, the risk of carcinogenesis does not increase.

Effect of Bundling and High Environmental Temperature on Neonatal Body Temperature

PEDIATRICS ◽  
1993 ◽  
Vol 92 (2) ◽  
pp. 238-240
Author(s):  
Tina L. Cheng ◽  
J. Colin Partridge
Keyword(s):  
Treatment Group ◽  
Body Temperature ◽  
Rectal Temperature ◽  
Environmental Temperature ◽  
Control Group ◽  
Age Group ◽  
Linear Rate ◽  
Term Newborns ◽  
The Mean ◽  
Experimental Group

Objective. The effect of bundling and ambient heat on newborn body temperature has not been systematically studied. It was hypothesized that bundling and warm environments can elevate the newborn's temperatures to the range that would prompt clinical concern of neonatal sepsis. Methods. Twenty well, term newborns more than 1 day old were assigned to the control group (one blanket; 24.0°C room) or the experimental group (five blankets and hat; 26.6°C room). Continuous rectal probe temperatures were monitored over a 2½hour period. Results. There were 8 control and 12 experimental newborns. The mean change in rectal temperature after 2½ hours was -0.04°C (SD ± 0.23) in control newborns and + 0.56°C (SD ± 0.12) in the treatment group (P &lt; .0001, t test). Temperatures in the treatment group rose, after an initial half-hour lag, at a linear rate of 0.27°C per hour without a plateau. Two newborns reached 38.0°C, a rectal temperature that may raise concern of infection. Conclusions. Bundling and warm environments can elevate newborn body temperature to the "febrile" range in this age group. Physicians treating neonates with elevated temperature should ask about bundling and environmental conditions to differentiate endogenous from exogenous "fevers."

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