Impact of Energy and Access Methods on Extrahepatic Tumor Spreading and the Ablation Zone: An Ex vivo Experiment Using a Subcapsular Tumor Model

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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Exploiting Tissue Dielectric Properties to Shape Microwave Thermal Ablation Zones

Sensors ◽

10.3390/s20143960 ◽

2020 ◽

Vol 20 (14) ◽

pp. 3960

Author(s):

Anna Bottiglieri ◽

Giuseppe Ruvio ◽

Martin O’Halloran ◽

Laura Farina

Keyword(s):

Adipose Tissue ◽

Dielectric Properties ◽

Thermal Ablation ◽

Ex Vivo ◽

Reference Scenario ◽

Target Tissue ◽

Ablation Zone ◽

Dielectric Characterization ◽

Clinical Scenarios ◽

Tissue Target

The dielectric characterization of tissue targets of microwave thermal ablation (MTA) have improved the efficacy and pre-procedural planning of treatment. In some clinical scenarios, the tissue target lies at the interface with an external layer of fat. The aim of this work is to investigate the influence of the dielectric contrast between fat and target tissue on the shape and size of the ablation zone. A 2.45 GHz monopole antenna is placed parallel to an interface modelled by fat and a tissue characterized by higher dielectric properties and powered at 30 and 60 W for 60 s. The performances of MTA are numerically investigated considering different interface scenarios (i.e., different widths of fat layer, shifts in the antenna alignment) and a homogeneous reference scenario. Experiments (N = 10) are conducted on ex vivo porcine tissue to validate the numerical results. Asymmetric heating patterns are obtained in the interface scenario, the ablation zone in the target tissue is two-fold to ten-fold the size of the zone in the adipose tissue, and up to four times larger than the homogenous scenario. The adipose tissue reflects the electromagnetic energy into the adjacent tissue target, reducing the heating in the opposite direction.

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03:36 PM Abstract No. 367 An ex vivo bench and perfused liver assessment and extension of the ablation zone by “EdgeBoost” with IR-Circle: a new bipolar ablation device

Journal of Vascular and Interventional Radiology ◽

10.1016/j.jvir.2018.12.440 ◽

2019 ◽

Vol 30 (3) ◽

pp. S162

Author(s):

K. Altoukhi ◽

J. Akhter ◽

A. Mekkawy ◽

N. Alzahrani ◽

S. Valle ◽

...

Keyword(s):

Ex Vivo ◽

Perfused Liver ◽

Ablation Zone ◽

Bipolar Ablation

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Abstract No. 504 Ex vivo evaluation of the effect of multiple electrode radiofrequency needle tip convergence on size of ablation zone

Journal of Vascular and Interventional Radiology ◽

10.1016/j.jvir.2019.12.565 ◽

2020 ◽

Vol 31 (3) ◽

pp. S222

Author(s):

Z. Abraham ◽

A. Nasirzadeh ◽

B. Mussari ◽

A. Menard ◽

E. Tarulli

Keyword(s):

Ex Vivo ◽

Ablation Zone ◽

Multiple Electrode

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Dendritic cells modified to express CD40 ligand elicit therapeutic immunity against preexisting murine tumors

Blood ◽

10.1182/blood.v96.1.91.013k19_91_99 ◽

2000 ◽

Vol 96 (1) ◽

pp. 91-99 ◽

Cited By ~ 1

Author(s):

Toshiaki Kikuchi ◽

Malcolm A. S. Moore ◽

Ronald G. Crystal

Keyword(s):

Dendritic Cells ◽

Cytotoxic T Lymphocyte ◽

Tumor Regression ◽

Ex Vivo ◽

Tumor Model ◽

Adenovirus Vector ◽

Cd40 Ligand ◽

Murine Tumors

CD40 ligand (CD40L) is essential for the initiation of antigen-specific T-cell responses. This study is based on the hypothesis that dendritic cells (DCs) genetically modified ex vivo to express CD40L will enhance in vivo presentation of tumor antigen to the cellular immune system with consequent induction of antitumor immunity to suppress tumor growth. To examine this concept, subcutaneous murine tumors were injected with bone marrow-derived DCs that had been modified in vitro with an adenovirus (Ad) vector expressing murine CD40L (AdmCD40L). In B16 (H-2b, melanoma) and CT26 (H-2d, colon cancer) murine models, intratumoral injection of 2 × 106 AdmCD40L-modified DCs (CD40L-DCs) to established (day 8) subcutaneous tumors resulted in sustained tumor regression and survival advantage. This antitumor effect was sustained when the number of CD40L-DCs were reduced 10-fold to 2 × 105. Analysis of spleens from CD40L-DC–treated animals demonstrated that CD40L-DCs injected into the subcutaneous CT26 flank tumors migrated to the spleen, resulting in activation of immune-relevant processes. Consistent with this concept, intratumoral administration of CD40L-DCs elicited tumor-specific cytotoxic T-lymphocyte responses, and the transfer of spleen cells from CD40L-DC–treated mice efficiently protected naive mice against a subsequent tumor challenge. In a distant 2-tumor model of metastatic disease, an untreated B16 tumor in the right flank regressed in parallel with a left B16 tumor treated with direct injection of CD40L-DCs. These results support the concept that genetic modification of DCs with a recombinant CD40L adenovirus vector may be a useful strategy for directly activating DCs for cancer immunotherapy.

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CWR22 Xenograft as an Ex Vivo Human Tumor Model for Prostate Cancer Gene Therapy

JNCI Journal of the National Cancer Institute ◽

10.1093/jnci/88.9.607 ◽

1996 ◽

Vol 88 (9) ◽

pp. 607-611 ◽

Cited By ~ 18

Author(s):

L. Cheng ◽

J. Sun ◽

T. G. Pretlow ◽

J. Culp ◽

N.-S. Yang

Keyword(s):

Prostate Cancer ◽

Gene Therapy ◽

Ex Vivo ◽

Human Tumor ◽

Tumor Model ◽

Cancer Gene Therapy ◽

Cancer Gene

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Anti-Tumoral and Anti-Angiogenic Effects of Low-Diluted Phenacetinum on Melanoma

Frontiers in Oncology ◽

10.3389/fonc.2021.597503 ◽

2021 ◽

Vol 11 ◽

Author(s):

Camille Fuselier ◽

Sandrine Quemener ◽

Eleonore Dufay ◽

Camille Bour ◽

Camille Boulagnon-Rombi ◽

...

Keyword(s):

Endothelial Cells ◽

Side Effects ◽

Ex Vivo ◽

Tumor Model ◽

Primary Cutaneous Melanoma ◽

Relieve Pain ◽

Melanoma Treatment ◽

Vertical Growth Phase

Melanoma is the most aggressive form of skin cancer and the most rapidly expanding cancer in terms of worldwide incidence. If primary cutaneous melanoma is mostly treated with a curative wide local excision, malignant melanoma has a poor prognosis and needs other therapeutic approaches. Angiogenesis is a normal physiological process essential in growth and development, but it also plays a crucial role in crossing from benign to advanced state in cancer. In melanoma progression, angiogenesis is widely involved during the vertical growth phase. Currently, no anti-angiogenic agents are efficient on their own, and combination of treatments will probably be the key to success. In the past, phenacetin was used as an analgesic to relieve pain, causing side effects at large dose and tumor-inducing in humans and animals. By contrast, Phenacetinum low-dilution is often used in skin febrile exanthema, patches profusely scattered on limbs, headache, or flushed face without side effects. Herein are described the in vitro, in vivo, and ex vivo anti-angiogenic and anti-tumoral potentials of Phenacetinum low-dilution in a B16F1 tumor model and endothelial cells. We demonstrate that low-diluted Phenacetinum inhibits in vivo tumor growth and tumor vascularization and thus increases the survival time of B16F1 melanoma induced-C57BL/6 mice. Moreover, Phenacetinum modulates the lung metastasis in a B16F10 induced model. Ex vivo and in vitro, we evidence that low-diluted Phenacetinum inhibits the migration and the recruitment of endothelial cells and leads to an imbalance in the pro-tumoral macrophages and to a structural malformation of the vascular network. All together these results demonstrate highly hopeful anti-tumoral, anti-metastatic, and anti-angiogenic effects of Phenacetinum low-dilution on melanoma. Continued studies are needed to preclinically validate Phenacetinum low-dilution as a complementary or therapeutic strategy for melanoma treatment.

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Human-specific GAPDH RT-qPCR is an accurate and sensitive method of xenograft metastasis quantification

10.1101/2020.07.16.207175 ◽

2020 ◽

Author(s):

Margaret L Dahn ◽

Cheryl A Dean ◽

Diana B Jo ◽

Krysta M Coyle ◽

Paola Marcato

Keyword(s):

Lung Metastasis ◽

Histological Analysis ◽

Ex Vivo ◽

Tumor Model ◽

Xenograft Tumor ◽

Thin Sections ◽

Xenograft Tumor Model ◽

Qpcr Method ◽

Xenograft Models ◽

Human Specific

AbstractMetastasis is the primary cause of cancer-related mortality. Having experimental models that accurately reflect changes in the metastatic burden is imperative for developing improved treatments and a better understanding of the disease. The murine xenograft tumor model mimics the human scenario and provides a platform for in vivo and ex vivo metastasis quantification analyses. Histological analysis of hematoxylin and eosin (H&E) stained thin sections has been the gold standard for quantifying metastasis ex vivo but gaining favor for its ease and accuracy is reverse transcription-qualitative polymerase chain reaction (RT-qPCR). Herein we directly compare histological and RT-qPCR-based methods for quantifying lung metastasis in a murine xenograft tumor model. Furthermore, we have introduced a variation of the RT-qPCR method; human-specific glyceraldehyde 3-phosphate dehydrogenase (GAPDH) RT-qPCR, which allows quantification of metastasis in xenograft models, without the requirement of overexpression of exogenous genes. Human-specific GAPDH RT-qPCR detected increased lung metastasis resulting from aldehyde dehydrogenase 1A3 (ALDH1A3) expression in MDA-MB-231 breast cancer cells orthotopically implanted in NOD/SCID mice. Further, in the xenograft tumor model, human-specific GAPDH RT-qPCR was more sensitive and cost-effective than quantification of lung metastasis by histological analysis of H&E stained fixed thin sections. The two assays were highly correlative in terms of determining relative metastatic burden, suggesting that the human-specific GAPDH RT-qPCR method could be used as a standard method for quantification of disseminated human cells in murine xenograft models.

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Evaluation of Tumor Response to Adjuvant Treatments using an Ex Vivo Culture of Breast Carcinoma Spheroids in a Microfluidic Device

10.1101/2021.05.19.21257378 ◽

2021 ◽

Author(s):

Hamidreza Aboulkheyr Es ◽

Amir Reza Aref ◽

Lobat Granpayeh ◽

Marzieh Ebrahimi ◽

Hossein Baharvand

Keyword(s):

Breast Cancer ◽

Microfluidic Device ◽

Ex Vivo ◽

3D Culture ◽

Tumor Model ◽

Metastatic Tumor ◽

Clinical State ◽

Chemotherapy Response ◽

Tumor Spheroids ◽

Molecular Features

Abstract Purpose Breast cancer is the leading cause of cancer-related death among women worldwide. Conventional chemotherapy is considered a clinical state of the art treatment; however, resistance or recurrence occurs among a considerable portion of these patients. Besides understanding the genomic alterations pattern of tumor cells and their association with drug resistance or response, the development of a reliable tumor models that reflect the major cellular and molecular features of tumors may aid with screening of candidate drugs and identification of appropriate treatment regimens. Here, we developed a simple and low-cost tumor model of breast cancer to screen library of chemotherapy agents in a pre-clinical setting. Methods we generated and cultured ex-vivo 3D culture of patient-derived tumor spheroids from both pre-treated primary and metastatic tumors using a partial digestion approach in a microfluidic device. We assessed chemotherapy response of the seven patient-derived breast tumor spheroids and expanded evaluation of drug sensitivity through molecular analysis of a small panel of genes. Results We observed various chemotherapy responses across primary and metastasis tumor samples. Interestingly, we demonstrated response to paclitaxel and doxorubicin and resistance to cisplatin in 2/3 metastatic tumor samples while most of the primary tumor were responsive to chemotherapy. Additionally, the expression of PIK3CA and loss of PTEN were associated to treatment resistance. Conclusion Our study suggests potential application of microfluidic-based cell culture technology coupled with patient derived tumor spheroids in prediction of treatment response in a personalized manner.

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