Treatment of Human Renal Cell Carcinoma with High-Energy Shock Waves–A New in vivo/in vitro Model

Roessler, Wolfgang; Rothgangel, Beate; Hofstaedter, Ferdinand

doi:10.1159/000282736

Cited by 6 publications

(2 citation statements)

References 12 publications

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“…In the past, many studies of HESW were conducted on different human and animal tumour cell lines, describing an alteration of the cell growth (7)(8)(9)(10)(11). The in vitro effects of shock waves are due to a suppression of cell proliferation correlated with an apoptotic cell death process; moreover, HESW treatment has been shown to cause a transient increase in cell membrane permeability by opening micropores (such as electroporation), allowing higher intracellular drug concentration (12)(13)(14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

High energy shock waves enhance the cytotoxic effect of doxorubicin and methotrexate to human osteosarcoma cell lines

Palmero

Berger²,

Venturi³

et al. 2006

Oncol Rep

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Abstract. Despite recent advances, the prognosis of relapsed osteosarcoma patients remains very poor. Application of high energy shock waves may change the tumour cell growth and increase the cytotoxic effect of in vivo and in vitro chemotherapeutic agents. We studied the effect of their association with doxorubicin or methotrexate on three in vitro osteosarcoma cell lines. The effect of these combinations on SJSA-1, MG-63 and HOS human osteosarcoma cell lines were evaluated through incubation with doxorubicin or methotrexate and high energy shock wave treatment with 1000 shots at 0.22 mJ/mm 2 and an evaluation of the cell number, cell proliferation and apoptosis at days 1, 3 and 6 from the start of treatment. The combination of high energy shock waves and doxorubicin induced a statistically significant advantage in terms of a decrease in cell number on the SJSA-1 and HOS cell lines, a decrease of cell proliferation on all three cell lines and an increase of apoptosis only on the SJSA-1 cell line. The combination of high energy shock waves with methotrexate induced a decrease of the cell number only in the SJSA-1 and in the HOS cell lines, of the cell proliferation in the SJSA-1 and in the MG-63 cell lines, and an increase of apoptosis only on the SJSA-1 cell line. In conclusion, these experiments show an interesting effect of high energy shock waves on osteosarcoma cell lines, which could lead to future studies of the in vivo effects of high energy shock waves in the murine model as well. IntroductionOsteosarcoma (OS) is the most frequent bone tumour and is most common between the ages of 15 and 25. A high number of patients have a high-grade tumour, which prognosis has dramatically improved from 10-15% to 65-70% in the last 25 years, thanks to the use of adjuvant and neoadjuvant chemotherapy (1,2). Nevertheless, despite continuing scientific research into the treatment, the prognosis of the patients with OS in metastatic relapse, especially to bones (3), is still very poor; even with a recently concluded Italian and Scandinavian phase II protocol including high-dose chemotherapy the 3-year overall survival and the 3-year disease free-survival rates were only 20% and 12% respectively (4).The search of new treatments for improving the survival of the patients without increasing the collateral effects of the chemotherapy has led us to study new ways to increase the chemo-sensitivity of the OS cells.High energy shock waves (HESW) are routinely used in clinical practise in orthopaedic and in urology to treat a number of different diseases, such as urinary stones, non-unions of the bone fractures, tennis elbow, calcifying tendonitis, pseudoarthrosis and necrosis of the femoral head (5,6).In the past, many studies of HESW were conducted on different human and animal tumour cell lines, describing an alteration of the cell growth (7-11). The in vitro effects of shock waves are due to a suppression of cell proliferation correlated with an apoptotic cell death process; moreover, HESW treatment has been shown to cause a t...

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Section: Introductionmentioning

confidence: 99%

High energy shock waves enhance the cytotoxic effect of doxorubicin and methotrexate to human osteosarcoma cell lines

Palmero

Berger²,

Venturi³

et al. 2006

Oncol Rep

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“…[1][2][3] The apparent feasibility of exposing a spatially limited region of the body to a potentially destructive form of mechanical energy has led to the idea of applying shock waves in tumor therapy. 4) Previous results have not necessarily been promising, in cases of shock wave therapy alone, [4][5][6][7][8] or in combination with various anti-cancer agents, for example, cisplatinum, [9][10][11][12][13] mitomycin C (MMC), 12,13) actinomycin D, 12) methotrexete 13) and adriamycin (ADR). 11,13,14) However, we have reported that the combination of focused shock waves and bleomycin (BLM) reduced the IC 50 of BLM to 1/10 000-1/100 000 in various human cancer cell lines, when compared to BLM alone.…”

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Mechanism of Anti‐tumor Effect of Combination of Bleomycin and Shock Waves

Kato¹,

Ioritani²,

Suzuki

et al. 2000

Japanese Journal of Cancer Research

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We have previously reported marked enhancement of the cytocidal effect of bleomycin (BLM) on cancer cell suspensions in vitro by the combination with shock waves. In this study, we evaluated the synergistic effects on cancer cell proliferation and apoptosis in solid tumors. A spherical piezoceramic element was used as the shock wave source, with a pressure peak of 40 MPa. A human colon cancer cell line, SW480 was implanted onto the back of nude mice. Two thousand shock waves were administered to the tumor immediately following an intravenous injection of BLM at a dose of one-tenth of the LD 50 . The tumor was extirpated at 3, 6, 12, 24, 72 h and 1 week following shock exposure. Cell proliferation and apoptosis were detected by Ki-67 using antibody MIB-1 and by the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick-end labeling (TUNEL) method. The lowest percentage (35.7%) of Ki-67-positive cells appeared 24 h following the treatment. The maximum apoptotic index was detected within 6 h following the treatment. Moreover, numerous large cells with enlarged nuclei were detected histologically. These results suggest that shock waves may enhance chemotherapeutic effects by increasing apoptosis and decreasing cell proliferation in the tumor tissue. Key words: Shock wave -Bleomycin -SW480 -TUNEL -Mitotic deathA focused underwater shock wave can exert a high acoustic intensity in deep portions of the body without causing damage to adjacent tissues because of its high permeability through the tissues.1-3) The apparent feasibility of exposing a spatially limited region of the body to a potentially destructive form of mechanical energy has led to the idea of applying shock waves in tumor therapy. 4)Previous results have not necessarily been promising, in cases of shock wave therapy alone, [4][5][6][7][8] or in combination with various anti-cancer agents, for example, cisplatinum, 9-13) mitomycin C (MMC), 12, 13) actinomycin D, 12) methotrexete 13) and adriamycin (ADR). 11, 13, 14) However, we have reported that the combination of focused shock waves and bleomycin (BLM) reduced the IC 50 of BLM to 1/10 000-1/100 000 in various human cancer cell lines, when compared to BLM alone. 15,16) This effect was detected even with a weak shock wave energy, which alone had almost no cytotoxic effect, and the degree of cytotoxicity enhancement was proportional to the amount of shock wave energy applied. 15,16) Immediately after shock wave exposure, cancer cells were examined under scanning and transmission electron microscopes. Numerous dimples (diameters distributed from 0.05 to 0.5 µm) became apparent on the cell surface.15, 16) These dimples were concluded to be pores penetrating through the cell membrane, because reagents such as propidium iodide and 5(6)-carboxyfluorescein could enter the cytoplasm of the cells treated with shock waves. The mechanism of this enhancement of chemotherapeutic effect was considered to be the entry of BLM molecules into cells through pores opened by the shock waves, but the details rem...

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High Energy Shock Waves (HESW) Enhance Paclitaxel Cytotoxicity in MCF-7 Cells

Frairia

Catalano

Fortunati

et al. 2003

Breast Cancer Res Treat

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High energy shock waves (HESW) produced by a piezoelectric generator were studied for their effect on human breast cancer cell (MCF-7) viability and sensitivity to paclitaxel. A dose-dependent impairment of cell viability was observed after HESW treatment (250-2000 shock waves, rate = 4/s, energy flux density = 0.25 mJ/mm2). Single treatment with shock waves produced no significant growth inhibition. Combined exposure to paclitaxel (ranging 0.1 nM to 20 microM) and shock waves (100, 500 and 1000 shots, respectively) resulted in a significant reduction of MCF-7 cell proliferation at day 3 after treatment in respect with cells treated with paclitaxel alone. Notably, a cell viability reduction of about 50% was obtained after combined treatment with HESW and 10 nM paclitaxel, in front of a reduction of only 40% using 10 microM paclitaxel alone. Moreover, an earlier induction as well as an enhancement of apoptotis was observed in cells subjected to combined treatment with shock waves and paclitaxel (200 nM; 20 microM). In conclusion, HESW can enhance paclitaxel cytotoxicity in MCF-7 cells, thus allowing the treatment with lower doses of drug.

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Treatment of Human Renal Cell Carcinoma with High-Energy Shock Waves–A New in vivo/in vitro Model

Cited by 6 publications

References 12 publications

High energy shock waves enhance the cytotoxic effect of doxorubicin and methotrexate to human osteosarcoma cell lines

High energy shock waves enhance the cytotoxic effect of doxorubicin and methotrexate to human osteosarcoma cell lines

Mechanism of Anti‐tumor Effect of Combination of Bleomycin and Shock Waves

High Energy Shock Waves (HESW) Enhance Paclitaxel Cytotoxicity in MCF-7 Cells

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