Combined Hyperthermia and Radiation Therapy for Treatment of Hepatocellular Carcinoma

Talaat, Roba M.; Abo-Zeid, Tamer M; Abo-Elfadl, Mahmoud T; El-maadawy, Eman A.; Hassanin, Mona M

doi:10.31557/apjcp.2019.20.8.2303

Cited by 9 publications

(11 citation statements)

References 36 publications

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“…Direct absorption of ultrasound by tissues also induces hyperthermia and has been a major factor in anti-cancer therapies 34 . Hyperthermia, alone or in combination with other therapeutic modalities such as radiation therapy, chemical drugs, or ablative ultrasound therapy has been shown to enhance HCC treatment 14 , 16 , 35 . Likewise, hyperthermia induced by ultrasound has been demonstrated in efficient drug delivery in tumors 36 .…”

Section: Discussionmentioning

confidence: 99%

“…Hyperthermia has long been used as an adjunctive radio- and chemo-sensitizing therapeutic agent for HCC treatment 13 – 15 . Hyperthermia has shown to enhance radiation response in HCC by increasing radiation-induced cytotoxicity and inhibiting DNA damage repair mechanisms 16 . Under the normal course of hyperthermia, the presence of blood vessels in the targeted tissue region buffers the adjacent cells from the intended tissue damage by allowing thermal energy to dissipate via blood flow 17 , 18 .…”

Section: Introductionmentioning

confidence: 99%

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Hydralazine augmented ultrasound hyperthermia for the treatment of hepatocellular carcinoma

Karmacharya

Sultan

Hunt

et al. 2021

Sci Rep

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This study investigates the use of hydralazine to enhance ultrasound hyperthermia for the treatment of hepatocellular carcinoma (HCC) by minimizing flow-mediated heat loss from the tumor. Murine HCC tumors were treated with a continuous mode ultrasound with or without an intravenous administration of hydralazine (5 mg/kg). Tumor blood flow and blood vessels were evaluated by contrast-enhanced ultrasound (CEUS) imaging and histology, respectively. Hydralazine markedly enhanced ultrasound hyperthermia through the disruption of tumor blood flow in HCC. Ultrasound treatment with hydralazine significantly reduced peak enhancement (PE), perfusion index (PI), and area under the curve (AUC) of the CEUS time-intensity curves by 91.9 ± 0.9%, 95.7 ± 0.7%, and 96.6 ± 0.5%, compared to 71.4 ± 1.9%, 84.7 ± 1.1%, and 85.6 ± 0.7% respectively without hydralazine. Tumor temperature measurements showed that the cumulative thermal dose delivered by ultrasound treatment with hydralazine (170.8 ± 11.8 min) was significantly higher than that without hydralazine (137.7 ± 10.7 min). Histological assessment of the ultrasound-treated tumors showed that hydralazine injection formed larger hemorrhagic pools and increased tumor vessel dilation consistent with CEUS observations illustrating the augmentation of hyperthermic effects by hydralazine. In conclusion, we demonstrated that ultrasound hyperthermia can be enhanced significantly by hydralazine in murine HCC tumors by modulating tumor blood flow. Future studies demonstrating the safety of the combined use of ultrasound and hydralazine would enable the clinical translation of the proposed technique.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Hydralazine augmented ultrasound hyperthermia for the treatment of hepatocellular carcinoma

Karmacharya

Sultan

Hunt

et al. 2021

Sci Rep

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“…When reaching con uence, monolayer cells were rinsed with phosphate buffered slaine (PBS) and harvested by trypsin/EDTA (Biowest) treatment. After treatment of cells with the formulations containg different concentration of HG and ST and incubation for 48 h at 37ºC, the plates were examined under the inverted microscope and proceeded for the MTT assay [25].…”

Section: Cell Viability Assaymentioning

confidence: 99%

Alginate/CaCO3 Hybrid Loaded with Sorafenib Tosylate and Gold Hexagons: A Model for Efficient Dual (Chemo-Radio) Treatment of HepG2 Cells

Sukkar

Shafaa

El–Nagdy

et al. 2021

Preprint

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In this work, we investigated the combinatorial cytotoxic actions of the chemotherapeutic drug (sorafenib tosylate, ST) in synergism with γ-radiation on human hepatocellular carcinoma (HepG2) cells. The novel radiosensitizer, hexagonal gold nanoparticles, was prepared and utilized To enhance the radiobiological response of HepG2 cells. A well-designed nanoporous alginate/CaCO3 hybrid was prepared as a biocompatible/biodegradable nanocarrier for co-delivery of the hydrophobic drug and the hydrophilic radiosensitizer to the cancer cells. Incubation of HepG2 cells with the nanoprobes followed by different doses (0, 3 or 6 Gy) of γ-radiation resulted in significant reduction of the cells viability as a result of the synergistic (chemo-radiation) cytotoxic actions.

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“… 4 , 5 Thermotherapy could improve the hypoxia inside the tumor and boots the radiation therapeutic effects. 6 , 7 …”

Section: Introductionmentioning

confidence: 99%

“…4,5 Thermotherapy could improve the hypoxia inside the tumor and boots the radiation therapeutic effects. 6,7 Heat shock has been suggested as a non-invasive and non-toxic alternative to induce gene expression locally using a heat-inducible promoter. 8,9 For example, Tang et al have demonstrated that a hetero gene with hsp70 promoter could be elevated to 10 to 500-fold over background by magnetic heat (43 °C).…”

Section: Introductionmentioning

confidence: 99%

Egr1/HSP70 Promoter-Driven Activation of Gene Expression for Synergistic Anti-Hepatoma Using PEI-MZF Nanoparticles and Radiation

Zhang¹,

Dong²,

Yan³

et al. 2022

IJN

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Introduction Spatially restricted gene expression circumvents the gene expression and gene vector problem by enabling localized amplification. The objective of this study is to construct a spatially restricted gene expression for liver cancer therapy based upon the MFH-absorbing properties of PEI- Mn 0.5 zn 0.5 Fe 2 o 4 , gene therapy and radiation. Methods Mn 0.5 zn 0.5 Fe 2 O 4 (MZF) magnetic nanoparticles were prepared by an improved chemical co-precipitation method, modified by polyethylene imine (PEI), and then the structure, modification characters, biocompatibility, temperature rise and control ability and binding efficiency of the plasmid were characterized. Then, the dual-promoter plasmid PCDNA3.1-EGR1-HSP70-HSVTK was constructed. The recombinant vectors were identified by enzyme digestion analysis and DNA sequencing. The TK gene expression level was detected by realtime-PCR assay in HEK293 cells. Also, the HSV-TK gene expression was detected in SMMC7721 cells with the help of PEI-Mn 0.5 Zn 0.5 Fe 2 O 4 . In vitro anti-tumor experiment, MTT assay and flow cytometry were used to evaluate the therapeutic effects of the cultured SMMC7721 cells treated by different ways. In vivo anti-tumor experiment, the xenografted mice were treated by different ways for three times to detect the antitumor effect. Results The Mn 0.5 Zn 0.5 Fe 2 O 4 magnetic nanoparticles could be successfully prepared through improved co-precipitation process and showed good biocompatibility. And PEI had been coated on MZF complex. The modified PEI-MZF presented favorable dispensability, responsibility to magnetism, good loading capability and transfect capability. Also, pCDNA3.1-Egr1-Hsp70-HSVTK plasmid had been constructed successfully and could be induced by heat and irradiation. It would be used for further target gene therapy research. The antitumor results in vitro showed: The therapeutic effects of nanosized PEI-MZF-HSV-TK complex could significantly inhibit the proliferation of cultured liver cancer cells (SMC7721), induce cell apoptosis and had a prominent cell cycle disturbance in the S phase in vitro. The results in vivo showed: The combined therapy induced by PEI-MZF-HSV-TK could inhabit the growth of hepatocellular carcinoma xenografts by killing and inhabiting the proliferation of the tumor cells. Conclusion The novel site-directed heat/radiation-inducible expression system based upon the hyperthermia (by MFH) and radiation possessed superior antitumor effect in vivo and in vitro.

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Combined Hyperthermia and Radiation Therapy for Treatment of Hepatocellular Carcinoma

Cited by 9 publications

References 36 publications

Hydralazine augmented ultrasound hyperthermia for the treatment of hepatocellular carcinoma

Hydralazine augmented ultrasound hyperthermia for the treatment of hepatocellular carcinoma

Alginate/CaCO3 Hybrid Loaded with Sorafenib Tosylate and Gold Hexagons: A Model for Efficient Dual (Chemo-Radio) Treatment of HepG2 Cells

Egr1/HSP70 Promoter-Driven Activation of Gene Expression for Synergistic Anti-Hepatoma Using PEI-MZF Nanoparticles and Radiation

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