Radiofrequency ablation (RFA)-induced systemic tumor growth can be reduced by suppression of resultant heat shock proteins

Ahmed, Muneeb; Kumar, Gaurav; Gourevitch, Svetlana; Levchenko, Tatyana; Galun, Eithan; Torchilin, Vladimir P.; Goldberg, S. Nahum

doi:10.1080/02656736.2018.1462535

Cited by 32 publications

(30 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Heat shock protein expression was mainly observed in the periablational rim, as expected, where the temperature was in the scope of nonlethal thermal injuries. These results were consistent with the research findings of Ahmed et al, which showed that hepatic radiofrequency ablation heating parameters alter periablational HSP, which can influence and stimulate distant tumor growth. Modulation of radiofrequency heating parameters alone or in combination with adjuvant HSP inhibition can reduce unwanted, off‐target systemic tumorigenic effects.…”

Section: Discussionsupporting

confidence: 93%

“…Therefore, this study combined an HSP90 inhibitor with MWA to determine the effect on tumor growth and the end point survival time in mice, and the results showed that combination treatment could reduce the tumor growth rate and prolong the end point survival time. These findings were closely related to the increase in the tumor necrosis range and immunohistochemical staining results observed in previous studies More importantly, although MWA prolonged the tumor growth time and terminal survival time compared to ganetespib, ganetespib alone showed greater survival benefits than the no‐treatment group, indicating that tumors were independently susceptible to ganetespib …”

Section: Discussionsupporting

confidence: 82%

See 1 more Smart Citation

Hepatic Microwave Ablation–Induced Tumor Destruction and Animal End Point Survival Can Be Improved by Suppression of Heat Shock Protein 90

Zhai

Zhou

Dou

et al. 2019

J of Ultrasound Medicine

View full text Add to dashboard Cite

Objectives-To investigate the effect of heat shock protein 90 (HSP90) modulation on tumor necrosis, apoptosis, tumor growth delay, and end point survival by combining microwave ablation (MWA) with an HSP90 inhibitor in a nude mouse model.Methods-This study was approved by the Ethics Committee. Forty mice with HepG2 subcutaneous xenograft tumors (10 AE 1 mm) were randomized into 4 groups: (1) no treatment, (2) MWA only, (3) the HSP90 inhibitor ganetespib only, and (4) ganetespib combined with MWA. Tumors were harvested 24 hours after treatment, and gross coagulation diameters were measured. The effect of ganetespib on HSP90 and caspase 3 expression in the periablational rim was assessed. Another 40 mice with the same tumors and groupings were observed after treatment. Tumor growth curve and Kaplan-Meier survival analyses were performed with a tumor diameter of 2.2 cm and 40 days of survival as the defined survival end points.Results-Combination treatment significantly increased the coagulation size compared to tumors treated with MWA or ganetespib alone (P < 0.05). The combination of MWA and ganetespib decreased HSP90 expression and increased cleaved caspase 3 expression 24 hours after treatment. Compared with MWA or ganetespib only, combination treatment could lengthen the end point survival and reduce the tumor growth rate.Conclusions-Modulation of HSP production can improve MWA-induced tumor apoptosis and destruction, reduce residual tumor growth rates, and prolong end point survival.

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 82%

Hepatic Microwave Ablation–Induced Tumor Destruction and Animal End Point Survival Can Be Improved by Suppression of Heat Shock Protein 90

Zhai

Zhou

Dou

et al. 2019

J of Ultrasound Medicine

View full text Add to dashboard Cite

show abstract

“…7 Schematic diagram shows that collagen I initiates ERK signaling to accelerate the aggressive progression of residual HCC cells after sublethal RFA, which could be reversed by sorafenib. More factors implicated in post-inflammation reaction after RFA promote tumor progression of residual HCC, which has been reported by the other authors [ 14 , 15 , 49 , 50 ] …”

Section: Discussionsupporting

confidence: 64%

“…This study has several limitations. First, besides collagen I, we could not exclude the other factors in post-inflammation reaction after RFA that influence tumor progression of residual HCC [ 14 , 15 , 49 , 50 ], such as RFA-induced tumor-specific T-cell reaction, a Th1 cytokine pattern after RFA, heat shock proteins, periablational cellular infiltration. Second, we did not identify the source of collagen I.…”

Section: Discussionmentioning

confidence: 99%

Extracellular matrix collagen I promotes the tumor progression of residual hepatocellular carcinoma after heat treatment

Zhang

Lin

et al. 2018

BMC Cancer

View full text Add to dashboard Cite

BackgroundAccelerated malignant behaviors induced by insufficient thermal ablation have been increasingly reported, however, the exact mechanisms are still unclear. Here, we investigated the importance of the extracellular matrix (ECM) in modulating the progression of residual hepatocellular carcinoma (HCC) after heat treatment.MethodsHeat-exposed residual HCC cells were cultured in different ECM gels. We used basement membrane gel (Matrigel) to simulate the normal microenvironment and collagen I to model the pathological stromal ECM. The alterations of morphology and parameters of proliferation, epithelial-mesenchymal transition (EMT) and stemness were analyzed in vitro and in vivo.ResultsIncreased collagen I deposition was observed at the periablational zone after incomplete RFA of HCC in a xenograft model. The markers of cell proliferation, EMT, motility and progenitor-like traits of heat-exposed residual HCC cells were significantly induced by collagen I as compared to Matrigel (p values all < 0.05). Importantly, collagen I induced the activation of ERK phosphorylation in heat-exposed residual HCC cells. ERK1/2 inhibitor reversed the collagen I-promoted ERK phosphorylation, cell proliferative, protrusive and spindle-like appearance of heat-treated residual HCC cells in vitro. Moreover, collagen I promoted the in vivo tumor progression of heat-exposed residual HCC cells, and sorafenib markedly reversed the collagen I-mediated protumor effects.ConclusionsOur findings demonstrate that collagen I could enhance the aggressive progression of residual HCC cells after suboptimal heat treatment and sorafenib may be a treatment approach to thwart this process.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4820-9) contains supplementary material, which is available to authorized users.

show abstract

“…35 Nonetheless modulation of RF heating parameters alone or in combination with adjuvant heat-shock proteins inhibition, STAT3 inhibition, or simple cyclooxygenase-2 selective non-steroidal antiinflammatory drugs can mitigate or reduce unwanted, off-target systemic tumorigenic effects. 36 Nevertheless, there may be a precarious and poorly understood balance between partial ablation or embolization inducing a tumorigenic response vs. an immune regression. Tipping this balance via pharmacomodulation may more fully recognize the preclinical promise and augmentation of HCC immunomodulation combined with local and regional image guided tools.…”

Section: B Amentioning

confidence: 99%

Combined locoregional-immunotherapy for liver cancer

Greten

Mauda-Havakuk

Heinrich

et al. 2019

Journal of Hepatology

163

123

View full text Add to dashboard Cite

Locoregional therapies are commonly used to treat patients with hepatocellular carcinoma. It has been noted for many years that locoregional therapies may have additional systemic effects other than simple tumour elimination. Immunological ''side effects" have been described in response to locoregional therapies in animal studies and in patients. With the advent of immunotherapy for hepatocellular carcinoma, there is increasing interest in determining the best way to combine immunotherapy with locoregional therapies. Herein, we provide a compact summary of answered and unanswered questions in the field, including: What animal model is best suited to test combined immune-locoregional treatments? How does tumour cell death affect immune responses? What type of immune responses have been observed in patients treated with different types of locoregional therapies? What can be surmised from the results of the first study testing the combination of locoregional therapy with immune checkpoint blockade? Finally, we discuss the outlook for this rapidly growing area of research, focussing on the issues which must be overcome to bridge the gap between interventional radiology and cancer immunology. Published by Elsevier B.V. on behalf of European Association for the Study of the Liver.

show abstract

Radiofrequency ablation (RFA)-induced systemic tumor growth can be reduced by suppression of resultant heat shock proteins

Abstract: Hepatic RF heating parameters alter periablational HSP70, which can influence and stimulate distant tumor growth. Modulation of RF heating parameters alone or in combination with adjuvant HSP inhibition can reduce unwanted, off-target systemic tumorigenic effects.

Cited by 32 publications

References 32 publications

Hepatic Microwave Ablation–Induced Tumor Destruction and Animal End Point Survival Can Be Improved by Suppression of Heat Shock Protein 90

Hepatic Microwave Ablation–Induced Tumor Destruction and Animal End Point Survival Can Be Improved by Suppression of Heat Shock Protein 90

Extracellular matrix collagen I promotes the tumor progression of residual hepatocellular carcinoma after heat treatment

Combined locoregional-immunotherapy for liver cancer

Contact Info

Product

Resources

About