Percutaneous liquid ablation agent for tumor treatment and drug delivery

Percutaneous locoregional therapies (LRTs), such as thermal ablation, are performed to limit the progression of hepatocellular carcinoma (HCC) and offer a bridge for patients waiting for liver transplantation. However, physiological challenges related to tumor location, size, and existence of multiple lesions as well as safety concerns related to potential thermal injury to adjacent tissues may preclude the use of thermal ablation or lead to its failure. Here, we showed a successful injection of an ionic liquid into tissue under image guidance, ablation of tumors in response to the injected ionic liquid, and persistence (28 days) of coinjected chemotherapy with the ionic liquid in the ablation zone. In a rat HCC model, the rabbit VX2 liver tumor model, and 12 human resected tumors, injection of the ionic liquid led to consistent tumor ablation. Combining the ionic liquid with the chemotherapy agent, doxorubicin, resulted in synergistic cytotoxicity when tested with cultured HCC cells and uniform drug distribution throughout the ablation zone when percutaneously injected into liver tumors in the rabbit liver tumor model. Because this ionic liquid preparation is simple to use, is efficacious, and has a low cost, we propose that this new LRT may bridge more patients to liver transplantation.

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A transgenic zebrafish liver tumor model with inducible Myc expression reveals conserved Myc signatures with mammalian liver tumors

Disease Models & Mechanisms ◽

10.1242/dmm.010462 ◽

2012 ◽

Vol 6 (2) ◽

pp. 414-423 ◽

Cited By ~ 52

Author(s):

Z. Li ◽

W. Zheng ◽

Z. Wang ◽

Z. Zeng ◽

H. Zhan ◽

...

Keyword(s):

Liver Tumor ◽

Liver Tumors ◽

Tumor Model ◽

Transgenic Zebrafish ◽

Mammalian Liver ◽

Zebrafish Liver

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Mapping of drug distribution in the rabbit liver tumor model by complementary fluorescence and mass spectrometry imaging

Journal of Controlled Release ◽

10.1016/j.jconrel.2017.10.042 ◽

2018 ◽

Vol 269 ◽

pp. 128-135 ◽

Cited By ~ 6

Author(s):

Katrin Fuchs ◽

Andras Kiss ◽

Pierre E. Bize ◽

Rafael Duran ◽

Alban Denys ◽

...

Keyword(s):

Mass Spectrometry ◽

Liver Tumor ◽

Mass Spectrometry Imaging ◽

Drug Distribution ◽

Tumor Model ◽

Rabbit Liver

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PL-019 Effect of early exercise on autophagy of liver tumor in mice

Exercise Biochemistry Review ◽

10.14428/ebr.v1i1.8223 ◽

2018 ◽

Vol 1 (1) ◽

Author(s):

Ning Jiang ◽

Zhe Wang ◽

Jing Li ◽

Xinghao Wang

Keyword(s):

Exercise Training ◽

Liver Tumor ◽

Liver Tumors ◽

Hepatoma Cell ◽

Tumor Model ◽

Inflammatory Cells ◽

Exercise Group ◽

Control Group ◽

Early Exercise ◽

Tumor Group

Objective To investigate whether the liver autophagy level can be altered by pre exercise training in mice liver tumors. Methods 40 Male C57BL/6J mice aged 7 months were randomly divided into 2 groups: control group (YC) and exercise group (YE). YE were exercised on a treadmill for 12 weeks (12m/min). After12 weeks each group was randomly divided into two groups. The tumor model was constructed by injection of HEPA1- 6 mouse hepatoma cell into liver tissue.Then the groups were control group (YC), exercise group (YE), tumor group (YCT), exercise tumor group (YET).The experimental samples were prepared on the 13 day after the tumor model was constructed. the hematoxylin and eosin stain of the liver was observed.The expression of autophagy related protein BECLIN1, LC3-II and ATG5 in liver tissues of mice was detected by Western blot. Results Compared with YCT group,the boundary of inflammatory cells and tumor cells in YET group was clear with normal cells.Compared with YCT group, the expression levels of BECLIN1, LC3-II and ATG5 in liver tissue of YET group were significantly higher (p < 0.01, P < 0.01, P < 0.05). Conclusions Early exercise can help the 7 month old mice to resist the occurrence and development of the liver tumor. It's probably associated with increased level of autophagy in the liver by early exercise training.

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Advancement to the clinic of an RNAi therapeutic for solid tumors

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.3585 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 3585-3585

Author(s):

D. Bumcrot ◽

I. Toudjarska ◽

A. Judge ◽

J. Brodsky ◽

E. Ambegia ◽

...

Keyword(s):

Solid Tumors ◽

Liver Tumor ◽

Liver Tumors ◽

Tumor Model ◽

Tumor Burden ◽

Systemic Administration ◽

Primary Hepatocellular Carcinoma ◽

Human Hepatoma Cells ◽

Lipid Particle

3585 Background: Malignancies of the liver, including primary (hepatocellular carcinoma) and secondary (metastatic) tumors, represent a significant unmet medical need. We are developing a therapeutic for solid tumors involving the liver that is comprised of lipid particle-formulated short interfering RNAs (siRNAs) targeting VEGF and the mitotic kinesin, KSP (Eg5). For each target, potent siRNA duplexes were selected following extensive screening in tissue culture cells. Efficacy was demonstrated in a mouse liver tumor model. Methods: To assess efficacy in vivo, a stable nucleic acid lipid particle (SNALP) formulation was developed based on similar formulations previously shown to silence liver-expressed genes via systemic administration in multiple species. A SNALP-formulated combination of the KSP and VEGF siRNAs (referred to as ALN-VSP01) was tested in an orthotopic liver tumor model in which human hepatoma cells (Hep3B) are implanted directly into the livers of immunocompromised mice. Results: Intravenous administration of ALN-VSP01 leads to dose-dependent inhibition of both KSP and VEGF expression in established liver tumors. This was accompanied by the formation of numerous aberrant mitotic figures (“monoasters”) in tumor cells indicative of the pharmacologic inhibition of KSP. In addition, tumor growth was significantly inhibited by a course of ALN-VSP01 treatment, and ALN-VSP01 treatment provided a clear survival benefit even when treatment was initiated in animals with a significant tumor burden. As a control, a SNALP-formulated siRNA targeting Luciferase was administered and shown to have no effect in these studies. Conclusions: Systemic administration of ALN-VSP01 exhibited clear efficacy in a mouse orthotopic liver tumor model. Clinical testing of ALN-VSP01 is expected to initiate in early 2009. [Table: see text]

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Liver tumor laser ablation – increase in the subacute ablation lesion volume detected with post procedural MRI

Acta Radiologica ◽

10.3109/02841851003694783 ◽

2010 ◽

Vol 51 (5) ◽

pp. 505-511 ◽

Cited By ~ 7

Author(s):

Roberto Blanco Sequeiros ◽

Juho Kariniemi ◽

Risto Ojala ◽

Li Chengli ◽

Marianne Haapea ◽

...

Keyword(s):

Laser Ablation ◽

Liver Tumor ◽

Liver Tumors ◽

Image Data ◽

Initial Therapy ◽

Tissue Response ◽

Lesion Volume ◽

Ablation Zone ◽

Ablation Volume ◽

Contrast Enhanced

Background: The use of image-guided thermoablative methods in liver tumor treatment has expanded rapidly due to encouraging results and advanced imaging. However, little is known about the treatment-induced tissue response and effects on imaging findings during the subacute post procedural period. Purpose: To study the development of subacute ablation zone volume with magnetic resonance imaging (MRI) after laser-mediated liver tumor thermal therapy. Material and Methods: In all, 16 laser ablations were performed on 16 liver tumors resulting in 16 ablation zones in 11 consecutive patients. A low-field 0.23 T C-arm MRI scanner was used for imaging and procedural guidance. Repeated dynamic contrast-enhanced T1, contrast-enhanced T1 FSE, and T2 FSE studies of liver were performed at 0 and 72 h after the procedure. Ablation zone volumes were registered from the acquired image data. Results: MRI scans showed a significant increase of ablation volume in all imaging sequences obtained at 72 h after the initial therapy. Conclusion: After laser ablation, there is a progressive perfusion decrease in the ablation site leading to an increase in the ablation volume. Post procedural baseline MRI at 72 h from the treatment provides more precise information about the ablation result than can be obtained with immediate post procedural MRI.

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