Theranostic liposomes as nanodelivered chemotherapeutics enhanced the microwave ablation of hepatocellular carcinoma

Aim: This study aimed to develop indocyanine green- and doxorubicin-loaded liposomes (DILPs) as theranostic nanoplatform for the detection of hepatocellular carcinoma (HCC) and as an efficient chemotherapeutic to enhance microwave ablation. Materials & methods: DILPs were synthesized and thoroughly characterized. Biocompatibility, tumor uptake and accumulation, and synergistic ablation-chemotherapeutic efficiency were systematically explored in them. In addition, human HCC surgical samples were used to test the affinity of DILPs for HCC. Results: The combination of microwave ablation and DILPs enhanced the ablation efficiency of HCC with apparent tumor inhibition. DILPs exhibited excellent diagnostic ability and could detect 2.5-mm HCC lesions via optoacoustic tomography imaging. DILPs had better affinity for human HCC surgical samples compared with normal liver tissue. Conclusion: Theranostic DILPs could serve as promising nanoparticles for treatment and management of HCC in the clinic.

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Glutathione and GSH-dependent enzymes in patients with liver cirrhosis and hepatocellular carcinoma.

Acta Biochimica Polonica ◽

10.18388/abp.2006_3384 ◽

2006 ◽

Vol 53 (1) ◽

pp. 237-241 ◽

Cited By ~ 61

Author(s):

Hanna Czeczot ◽

Dorota Scibior ◽

Michał Skrzycki ◽

Małgorzata Podsiad

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Tissue ◽

Normal Liver ◽

Cancer Tissue ◽

Glutathione Level ◽

Normal Tissues ◽

Control Tissue ◽

Cirrhotic Tissue ◽

Cancer Tissues ◽

Gst Activity

We investigated glutathione level, activities of selenium independent GSH peroxidase, selenium dependent GSH peroxidase, GSH S-transferase, GSH reductase and the rate of lipid peroxidation expressed as the level of malondialdehyde in liver tissues obtained from patients diagnosed with cirrhosis or hepatocellular carcinoma. GSH level was found to be lower in malignant tissues compared to adjacent normal tissues and it was higher in cancer than in cirrhotic tissue. Non-Se-GSH-Px activity was lower in cancer tissue compared with adjacent normal liver or cirrhotic tissue, while Se-GSH-Px activity in cancer was found to be similar to its activity in cirrhotic tissue and lower compared to control tissue. An increase in GST activity was observed in cirrhotic tissue compared with cancer tissue, whereas the GST activity in cancer was lower than in adjacent normal tissue. The activity of GSH-R was similar in cirrhotic and cancer tissues, but higher in cancer tissue compared to control liver tissue. An increased level of MDA was found in cancer tissue in comparison with control tissue, besides its level was higher in cancer tissue than in cirrhotic tissue. Our results show that the antioxidant system of cirrhosis and hepatocellular carcinoma is severely impaired. This is associated with changes of glutathione level and activities of GSH-dependent enzymes in liver tissue. GSH and enzymes cooperating with it are important factors in the process of liver diseases development.

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Elasticity Characterization of Liver Cancers Using Shear Wave Ultrasound Elastography: Comparison Between Hepatocellular Carcinoma and Liver Metastasis

Journal of Diagnostic Medical Sonography ◽

10.1177/8756479317733713 ◽

2017 ◽

Vol 33 (6) ◽

pp. 481-488 ◽

Cited By ~ 4

Author(s):

Kah Lai Choong ◽

Yin How Wong ◽

Chai Hong Yeong ◽

Gnana Kumar Gnanasuntharam ◽

Khean Lee Goh ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Metastasis ◽

Shear Wave ◽

Liver Tissue ◽

Normal Liver ◽

Ultrasound Elastography ◽

Normal Liver Tissue ◽

Tissue Elasticity ◽

Liver Cancers

Purpose: This was a feasibility study of shear wave ultrasound elastography for characterization of liver tumors and to compare the tissue elasticity values of hepatocellular carcinoma (HCC), liver metastases, and normal liver tissues. Methods: Forty-one patients and 30 healthy volunteers were recruited and categorized into HCC, liver metastasis, and control groups based on their computed tomography and sonographic examinations. Elasticity values of different groups were compared statistically. Results: Mean (standard deviation) elasticity values for HCC, liver metastasis, and normal liver tissue were 51.45 (14.96), 49.89 (13.82), and 6.63 (1.65) kilopascal, respectively. Statistically significant differences were found between the elasticity values of HCC and liver metastasis with normal liver tissue. Based on the receiver operating characteristics analysis, 18.25 kilopascal may differentiate the malignant focal liver lesions from the normal liver tissue with both sensitivity and specificity of 100%. Conclusion: Shear wave ultrasound elastography may be able to differentiate HCC and liver metastasis from normal liver tissue based on the tissue elasticity values.

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High expression of Janus kinase 2 in background normal liver tissue of resected hepatocellular carcinoma is associated with worse prognosis

Oncology Reports ◽

10.3892/or.2014.3621 ◽

2014 ◽

Vol 33 (2) ◽

pp. 767-773 ◽

Cited By ~ 2

Author(s):

FUMINORI SONOHARA ◽

SHUJI NOMOTO ◽

YOSHIKUNI INOKAWA ◽

MITSUHIRO HISHIDA ◽

NAO TAKANO ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Tissue ◽

Normal Liver ◽

Janus Kinase ◽

High Expression ◽

Normal Liver Tissue ◽

Janus Kinase 2 ◽

Worse Prognosis

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Upregulation of Spondin-2 protein expression correlates with poor prognosis in hepatocellular carcinoma

Journal of International Medical Research ◽

10.1177/0300060518803232 ◽

2018 ◽

Vol 47 (2) ◽

pp. 569-579 ◽

Cited By ~ 5

Author(s):

Ying Feng ◽

Yilin Hu ◽

Qinsheng Mao ◽

Yibing Guo ◽

Yifei Liu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Protein Expression ◽

Liver Tissue ◽

Matrix Protein ◽

Cox Regression ◽

Normal Liver ◽

Prognostic Indicator ◽

Extracellular Matrix Protein ◽

Matched Pairs ◽

Cox Regression Analysis

Objective The aim of this study was to measure the extracellular matrix protein Spondin-2 (SPON2) in hepatocellular carcinoma (HCC) tissues and to determine its potential value as a prognostic indicator by assessing its correlation with clinicopathological variables and survival. Methods SPON2 mRNA expression was assessed in 20 matched pairs of HCC and non-cancerous liver tissues by quantitative reverse transcription-polymerase chain reaction analysis. SPON2 protein expression was determined in 107 matched pairs of HCC and normal liver tissue by immunohistochemical staining of tissue microarrays. Results Analysis of patient tissues and Oncomine datasets showed that SPON2 mRNA and SPON2 protein expression were both significantly upregulated in HCC tissues, compared with non-cancerous liver tissue; moreover, both correlated significantly with tumor size. Kaplan-Meier analysis revealed that HCC patients who showed high levels of cytoplasmic SPON2 protein had poorer survival following curative resection, compared with HCC patients who exhibited low protein expression levels. Multivariate Cox regression analysis showed that tumor thrombus and SPON2 protein expression both independently correlated with reduced survival in HCC patients. Conclusion Upregulated expression of SPON2 protein in tumor tissue could be an effective prognostic indicator for patients with HCC.

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Distribution Characteristics and Species Diversity of Bacteria in Hepatocellular Carcinoma Tissues

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2022.2869 ◽

2022 ◽

Vol 12 (1) ◽

pp. 97-104

Author(s):

Yeqing Fang ◽

Weili Zhang

Keyword(s):

Hepatocellular Carcinoma ◽

Species Diversity ◽

Liver Tissue ◽

Bacterial Species ◽

Normal Liver ◽

Normal Group ◽

Normal Liver Tissue ◽

Control Group ◽

Sequencing Data ◽

Liver Tissues

This study was to explore the differences in the distribution and species diversity of bacteria between hepatocellular carcinoma (HCC) tissues and normal liver tissues. 28 HCC patients treated with surgery were selected as the research objects (HCC group), and 19 healthy volunteers with normal physical examinations were included in the control group (Normal group). The tumor specimens were obtained by intraoperative and biopsy puncture, and a 16S ribosomal ribonucleic acid (rRNA) library was constructed. Based on the sequencing data obtained by the IlluminaHi Seq sequencing platform, the differences of bacteria in the liver tissues of the HCC group and the Normal group were analyzed at the level of phyla, family, and genus. The Ace, Chao1, and Shannon of the two groups were compared. The results showed that IlluminaHi Seq sequencing obtained a total of 11,714,659 valid sequences, with an average of 131,625 sequences per sample. The proportions of Bacteroidetes, Firmicutes, and Proteobacteria in HCC group and Normal group were 48.75% versus 34.16%, 37.44% versus 18.02%, and 10.85% versus 39.26%, respectively. The Bacteroidaceae, Prevotellaceae, Lachnospiraceae, and Ruminococcaceae accounted for 22.49%, 20.62%, 16.54%, and 19.93% in Normal group; while those in the HCC tissues accounted for 26.83%, 14.22%, 11.14%, and 13.18%, respectively. The dominant bacteria at the genus level in HCC group and Normal group were Bacteroides and Prevotella-9, with the proportions of 24.19% versus 26.04% and 14.19% versus 8.44%, respectively. The difference in operational taxonomic unit (OTU) numbers of HCC and Normal group were compared and analyzed, which were 1,266 and 1,082, respectively, and the number of common OTU in the two tissues was 875. The Ace in HCC tissue and normal liver tissue were 1063.8±66.79 and 1003.6±52.19, respectively. The Ace in HCC tissue was greater than that in normal liver tissue (P < 0.05). The Chao1 and Shannon in HCC tissue were 1022.9±67.74 and 5.4269±0.3608, respectively; while those in normal liver tissue were 1003.6±66.79 and 5.2842±0.9714, respectively. The Chao1 and Shannon in HCC tissues were much higher than those in Normal group (P < 0.05). It showed that there was no difference in the types of bacterial species in HCC tissues, but the proportions of their flora at the level of phyla, family, and genus changed greatly, which may be related to the occurrence of HCC. This study could provide a reference for the diagnosis and treatment of HCC.

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Capacity of proton beams in preserving normal liver tissue during proton beam therapy for hepatocellular carcinoma

Journal of Radiation Research ◽

10.1093/jrr/rraa098 ◽

2020 ◽

Vol 62 (1) ◽

pp. 133-141

Author(s):

Yu-Lun Tsai ◽

Hideyuki Takei ◽

Takashi Iizumi ◽

Toshiyuki Okumura ◽

Yuta Sekino ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Linear Regression ◽

Liver Tissue ◽

Normal Liver ◽

Proton Beam Therapy ◽

Left Lobe ◽

Clinical Factors ◽

Proton Beams ◽

Preservation Rate ◽

Significant Factors

Abstract Unirradiated liver volume (ULV) preservation rate is an important factor associated with radiation-induced liver disease (RILD) in patients with hepatocellular carcinoma (HCC) undergoing proton beam therapy (PBT). The purpose of this study is to identify the predictors for ULV preservation and quantify the capacity of proton beams in normal liver sparing during PBT. We reviewed planning data of 92 patients with single intrahepatic HCC tumors undergoing PBT. The potential clinical and planning factors that may affect ULV preservation were involved in multiple linear regression for ULV preservation rate. The significant factors were determined to be predictors and their influences were quantified. The median ULV preservation rate was 62.08%. All the assessed clinical factors showed significant effects on ULV preservation rate: clinical target volume (CTV), P < 0.001; portal vein tumor thrombosis (PVTT), P = 0.010; left lobe tumor, P = 0.010. In contrast, none of the planning factors demonstrated significance. The coefficients of significant factors in multiple linear regression were 60.85 for intercept, −0.02 for CTV, −9.01 for PVTT and 8.31 for left lobe tumors. The capacity of proton beams to spare normal liver tissue during PBT for HCC is mainly affected by clinical factors. The baseline of the ULV preservation rate is 60.85%, decreasing 0.02% with each milliliter of CTV increase and 9.01% for tumors with PVTT, and increasing 8.31% for tumors limited to the left lobe. Further clinical studies should be carried out to correlate our dosimetric findings with clinical outcomes.

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