High-energy Shock Waves Treatment Research Articles

The use of high-energy shock wave treatment as pre-activation of sintering high-entropy solid solutions of transition metal borides and carbides

Synthesis of solid solutions of transition metal borides (NbB2, TaB2, HfB2 and ZrB2) and carbides (NbC, TaC, HfC, ZrC and VC) was carried out via sintering the individual components without applying pressure. To activate the interaction of the components, the initial powders were processed by high-energy shock wave treatment (HESWT). HESWT enables the formation of homogeneous solid solution for a mixture of carbides; however, this method did not give the desired results for a mixture of transition metal borides, likely due to the higher strength of borides crystal lattice in comparison with carbides.

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

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.

Feasibility of cord blood stem cell manipulation with high-energy shock waves: An in vitro and in vivo study

Cord blood CD34+ cells are more uncommitted than their adult counterparts as they can be more easily maintained and expanded in vitro and transduced with lentiviral vectors. The aim of this study was to evaluate whether pretreatment with high-energy shock waves (HESW) could further enhance the expansion of cord blood progenitors and the transduction efficiency with lentiviral vectors. Human cord blood CD34+ cells underwent HESW treatment with a wide range of energy and number of shots (from 0.22 mJ/mm2 to 0.43 mJ/mm2 and from 200 to 1500 shots). Cells were then evaluated both for their in vitro expansion ability and in vivo engraftment in primary, secondary, and tertiary NOD/SCID mice. The transduction efficiency with a lentiviral vector (LV) was also evaluated in vitro and in vivo. Cell viability following HESW ranged from 75 to 92%. Pretreatment with HESW significantly improved early progenitor cell expansion after short-term suspension culture. Upon transplantation in primary NOD/SCID mice, the HESW treatment enhanced progenitor cell engraftment (total human CD45(+)CD34+ cells were 10% in controls and 14.5% following HESW, human CD45(+)CD34(+)CD38(-) cells were 0.87% in controls and 1.8% following HESW). HESW treatment enhanced the transduction of a GFP+ lentiviral vector (e.g., at day 42 of culture 6.5% GFP+ cells in LV-treated cell cultures compared to 11.4% of GFP+ cells in HESW-treated cell cultures). The percentage of human GFP+ cell engrafting NOD/SCID mice was similar (34% vs 26.4% in controls); however, the total number of human cells engrafted after HESW was higher (39.6% vs 15%). The pretreatment of CD34+ cells with HESW represents a new method to manipulate the CD34+ population without interfering with their ability to both expand and engraft and it might be considered as a tool for genetic approaches.

Shock-Wave Therapy for Plantar Fasciitis

To The Editor: I read with great interest the article, “Electrohydraulic High-Energy Shock-Wave Treatment for Chronic Plantar Fasciitis” by Ogden et al. (2004;86:2216-28). I congratulate them for reporting the results of the FDA trial, which, to a vast extent, had been published earlier6,7. Some points remain open for discussion. 1. The alleged efficacy of this singledose, high-energy, anesthetically based treatment has already been discussed exhaustively by Buchbinder et al.3 in 2002. Regarding the HealthTronics-sponsored FDA trial2, Buchbinder et al. made the criticism that the presence of plantar fasciitis was determined solely on clinical grounds. Also, it was uncertain whether the two groups in the trial were comparable at baseline. In their previous paper, Ogden et al.6 defined overall success of treatment at twelve weeks as fulfillment of four of the following criteria: (1) a minimum 50% improvement over baseline in the investigator's assessment of pain (with a dolorimeter) and a score of £4 cm on a visual analogue scale; (2) a minimum 50% improvement over baseline in the subject's self-assessment of pain on first walking in the morning and a score of £4 cm on a visual analogue scale; (3) a minimum 1-point or greater improvement on a 5-point scale of distance walked without heel pain, or maintenance of a baseline assessment of no pain or minimal pain; and (4) no prescription of analgesics for pain in the treated heel between ten and twelve weeks after treatment. While success according to the three criteria other than the investigator's assessment of pain favored the active treatment, no difference was significant (subject's selfassessment of pain: 59.7% in the shock-wave group compared with 48.2% in the placebo group, p = 0.08; subject's self-assessment of activity level: 71.4% in the shock-wave group compared with 67.2% in … Corresponding author: John A. Ogden, MD Skeletal Educational Association 3435 Habersham Road N.W. Atlanta, GA 30305 orthozap{at}aol.com

Operative und nichtoperative Behandlung bei Pseudarthrosen

This review article summarizes our present knowledge on the physiological and on impaired processes in bone healing. All the clinical procedures applied are based on empirical clinical data and do not qualify as evidence-based medicine. Against this backdrop, high-energy shockwave treatment may well be a treatment alternative in selected patients who have already undergone surgery but are still suffering from a pseudarthrosis. For the time being, however, this form of therapy should be used only in clinical studies.

High energy shock waves (HESW) enhance paclitaxel cytotoxicity in MCF-7 cells.

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.

Enhancement of the Antitumor Effect by Combined Use of High‐energy Shock Waves and ATX‐70

The antitumor effects of high‐energy shock waves (HESW) in combination with ATX‐70 [a gallium‐porphyrin complex, 2,4‐bis(1‐decyloxyethyl)‐Ga(III)‐1,3,5,8‐tetramethylporphyrin‐6,7‐dipropionyi diaspartic acid] were investigated. In vitro, the cell damage to mouse MH134 hepatoma after HESW treatment was enhanced by adding ATX‐70. In vivo, HESW and ATX‐70 combination therapy inhibited cell growth. However, neither HESW treatment alone nor ATX‐70 treatment alone inhibited cell growth. These results imply that the antitumor effects of HESW and ATX‐70 combined therapy are caused by activation of ATX‐70 by HESW.

Cytocidal etfect of high energy shock wave on tumour cells enhanced with larger dose and multiple exposures

Cultured LLC-WRC256 (Walker rat carcinoma) cells were exposed to different doses of high energy shock waves (HESW). The immediate viabilities were 98% in the control cells, and 74%, 53% and 18% following 400, 800, and 1500 HESW treatment, respectively. Surviving cells in the 400 and 800-treated HESW demonstrated delayed upward growth rate curves, and the 1500 HESW-treated a downward curve. Agar clonogenic efficiencies for surviving cells were 36% (control), 20% (400 HESW), 15% (800 HESW) and 3% (1500 HESW). LLC-WRC256 tumours in Wistar rats were treated once every other day with 1500 HESW on a total of three occasions. Tumours treated with HESW grew more slowly (4.9 cm3) than those in the control (13.5 cm3). HESW fragmented cells and destroyed cell membranes and intracellular organelles. A histological examination of tumours treated with HESW demonstrated local haemorrhage with necrosis in the HESW focus area. Damage to the surrounding skin and soft tissue was slight and transient. These findings suggest that the growth of tumour cells can be suppressed in vitro and in vivo by treatment with HESW.

High-energy shock waves enhance hyperthermic response of tumors: effects on blood flow, energy metabolism, and tumor growth.

The ability to kill cancerous tissue by heating is often limited by heat lost to flowing blood. Recent studies demonstrate that high-energy shock waves (HESWs), when applied to solid tumors, destroy the tumor microvasculature and rapidly decrease blood flow. We hypothesized that impairment of tumor blood flow by HESWs might result in increased effectiveness of hyperthermia treatment. The purpose of our work was to determine whether HESWs enhance the response of tumors to hyperthermia. Seventy A-Mel-3 amelanotic hamster melanomas were exposed to either 700 HESWs (20 kV, 80 nanofarads), local hyperthermia (43.3 degrees C for 30 minutes), or a combination of both. Three, 12, or 24 hours later, tumor blood flow and adenosine triphosphate (ATP) concentrations were measured by [4-N-methyl-14C]iodoantipyrine autoradiography and quantitative ATP imaging bioluminescence, respectively. In separate experiments, the effects of the separate and combined treatments on tumor growth were studied in 52 animals. Combining HESWs and hyperthermia produced a significantly longer and more pronounced reduction of tumor and adjacent tissue perfusion than either HESWs or hyperthermia alone (P < .05). ATP concentrations were markedly reduced following HESW treatment alone and following the combined therapy compared with untreated controls (P < .05). Three hours after combined therapy, ATP concentrations were significantly below values measured after hyperthermia alone (P < .01). Tumor growth was delayed much more effectively by the combination of HESWs and hyperthermia than by either treatment alone (P < .001). Fifty-four percent of the animals receiving combined treatment showed complete local tumor cure over 52 days of observation, and 46% showed partial remission. The combination of HESWs and hyperthermia might be an effective new way of treating cancer, especially in patients who are not candidates for surgery. These results must be viewed cautiously, as the vasculature of human tumors seems to be less sensitive to hyperthermia than has been observed in experimental tumors.

Complete local tumor remission after therapy with extra-corporeally applied high-energy shock waves (HESW).

High-energy shock waves (HESW) have recently been proposed as a means of non-invasive tumor therapy. Here we report the first successful local treatment of experimental tumors by means of multifocal and reported application of HESW. The experiments were performed on 29 Syrian golden hamsters bearing amelanotic hamster melanomas in the dorsal skin. HESW, generated electrohydraulically, were applied multifocally to the center and to 5 sites on the margin of the tumors. A group of animals undergoing surgical resection and an untreated group served as controls. Complete remission of local tumor was achieved in more than 90% of the HESW-treated hamsters and in the same number of surgically treated animals, while untreated tumors continued to grow. Frequency of metastasis was the same in both groups after HESW treatment or surgery. Tumor therapy with multifocally and repeatedly applied HESW was thus as successful as surgery.

Effect of high-energy shock wave frequency on viability of malignant cell lines in vitro.

In this study, the effects of high-energy shock wave (HESW) frequency on the viability of three different malignant cell lines were evaluated using a piezo-electric generator. The cell lines studied were AR42-J, VX-2 and HeLa. These cells were targeted both in free suspension and immobilised in gelatine beads. All cell lines in free suspension were acutely sensitive to HESW over a range of frequencies. When cells were immobilised in gelatine, however, the effect on cell viability was not as pronounced. However, at frequencies of 80- and 160-Hz kill rates approaching 80 and 90%, respectively, were observed. Cell proliferation following HESW treatment was not adversely affected. This study demonstrates that single cell suspensions are not appropriate for assessing the in vitro cellular effects of HESW. However, even when cells were immobilised in gelatine, high-frequency HESW produced substantial kill rates. The effects of high-frequency HESW merit further evaluation particularly using in vivo tumour.

Effects of high-energy shock waves onmurine renal cell carcinoma

The effects of high-energy shock waves (HESW) on a murine renal cell carcinoma (RenCa) was investigated. In vitro exposure of tumor cells to HESW resulted in a dose-dependent reduction in cell viability as determined by trypan blue dye exclusion, plating efficiency, growth curve, and soft agar clonogenic assays. Activity of lactic dehydrogenase (LDH) was detected in the supernatant after the HESW treatment due to cellular destruction, and a dose-dependent increase in cytocidal effect was demonstrated. Ultrastructural changes with swelling and distorted cristae of mitochondria, vacuolation, ribosomal lysis, and chromatinolysis were observed in HESW-treated RenCa cells. Flow cytometric (FCM) study revealed that DNA content of RenCa cells diminished after 200 HESW treatment, and RNA content of tumor cells decreased markedly after 400 HESW treatments. Partial or complete inhibition of tumor growth was shown in both animal modalities of subcutaneous inoculation and intravenous injection with sequential lung metastases. This study stressed again that HESW may play a role in combinational protocol for the treatment of human renal cell carcinoma in certain circumstances.

Effects of high-energy shock waves combined with biological response modifiers or Adriamycin on a human kidney cancer xenograft

We have studied the effect of high-energy shock waves (HESW) alone or in combination with biological response modifiers (BRMs) or Adriamycin on the growth of the NU-1 human kidney cancer xenograft. When HESW are administered repeatedly (four sessions of 800 shock waves on days 0, 2, 4 and 6) a prolonged delay in tumor growth was found compared with that following a single administration. This effect was temporary, and several days after stopping the HESW administration the tumor regained its original growth potential (same doubling time). Tumor growth was suppressed for a longer period by the combination of 4 sessions of HESW and a single administration of Adriamycin, 5 mg/kg. Combination of HESW treatment with interferon alpha (5.0 ng/g body weight, three times/week) and tumor necrosis factor alpha (500 ng/g body weight, 5 days/week) s.c. around the tumor resulted in a complete cessation of tumor growth. While Adriamycin had an additive effect on HESW treatment, the combination with BRMs was highly synergistic.

Influence of high-energy shock waves and cisplatin on antitumor effect in murine bladder cancer

The potential application of high-energy shock waves (HESW) for control of experimental bladder cancer was investigated. Subcutaneous 3-d murine bladder cancer (MBT-2) in C3H mice were exposed to HESW alone (250 to 1,500 shocks) or in combination with cisplatin (5 to 10 mg/kg, i.p.). Although HESW alone showed no influence on tumor growth, HESW/cisplatin combination therapy suppressed tumor growth more than cisplatin alone. Subsequent studies revealed that an air-fluid interface relative to tumor location played a pivotal role for the chemosensitizing effect of HESW. HESW treatment was able to enhance the cisplatin cytotoxicity only when the tumors were placed adjacent to the air-fluid interface.

High energy shock waves do not affect either primary tumor growth or metastasis of prostate carcinoma, R3327-MatLyLu.

We investigated the possibility that extracorporeal high energy shock wave (HESW) treatment of solid tumors increased metastatic tumor cell spread using a rapidly metastasising rat prostate tumor variant (R3327-MatLyLu). Volume of HESW treated primary tumor, the volume of metastatic lymph nodes and the number of lung tumor nodules formed were compared with values in untreated control rats. HESW treatment resulted in marked hemorrhage and readily visible hematoma at the focal point of treatment. Tumor histology directly after treatment showed extravascular blood cells due to breakage of blood vessels. Contrary to previous reports we could not observe a delay in tumor growth rate in either small or medium sized tumors. More importantly the extent of metastatic spread was not influenced by HESW treatment.

The in vitro effect of electromagnetically generated shock waves (Lithostar) on the Dunning R3327 PAT-2 rat prostatic cancer cell-line. A potentiating effect on the in vitro cytotoxicity of vinblastin.

High energy shock wave lithotripsy has proven to be an effective tool in the management of renal calculi. The effects of electrohydraulically generated high energy shock waves (HESW) on tumor cells were described only recently. Here we present data on the experimental design for treatment of tumor cells, using electromagnetically generated shock waves. The determination of the focal area, in which pressures are at least 50% of the maximum pressure, appeared to be essential. In vitro HESW treatment resulted in a dose dependant anti-proliferative effect on Dunning R-3327 PAT-2 rat prostate cancer subline, determined by temporal growth curve analysis after plating of treated cells in soft agar. Furthermore, it was shown that HESW treatment had a potentiating effect on Vinblastin treatment. The combination of HESW with Vinblastin appeared to have an additive in vitro anti-proliferative effect on PAT-2 prostatic cancer cells.

The effect of high energy shock waves (HESW) on human bone marrow.

The effect of High energy shock waves (HESW) on the viability and proliferation of normal human bone marrow cells was evaluated. A dose dependent increase in cytotoxicity with an increase in the number of HESW was demonstrated. In general 700 HESW immediately reduced the cell viability of bone marrow cells by 50%. The CFU-GM assay provides a method to evaluate the effect of HESW on the proliferative capacity of bone marrow. Following HESW treatment the colony forming ability of trypan blue excluding cells also felt in a dose dependent fashion, but some variation in sensitivity was noted. By comparing the sensitivity of various cells, the cells of normal human bone marrow were felt to be less sensitive to HESW effects than those of other tissue cultured cells or malignant cell lines.