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High Energy Shock Waves (HESW) Inhibit Tumor Cell Proliferation and Potentiate Efficacy of Cytotoxic Agents
Accepted 497
498
ADRENAL CORTICAL CARCINOMA - THE CLEVELAND CLINIC EXPERIENCE. *Barry H. Bodie, Cleveland, OH (Presentation to be made by Dr. Bodie) . Between 1936 and 1986, seventy-two patients (35 males, 37 females) with histologically proven adrenal cortical carcinoma were seen at the Cleveland Clinic Foundation. Sixty-six of these patients were seen in the last 30 years. The average at presentation was 47 years (range 1.5 - 80 years). Four patients were children less than 18 years old. Thirty-six patients presented with a biochemically functional turror (9 males, 27 females), while the remainder had non-functioning turrors (26 males, 10 females). Metastatic disease was initially present in 41/72 patients (57%). Surgical extirpation of the turror was attempted in 60/72 patients. overall h.;o year survival in the series was 29% (31% in males, 29% in females). Patients with functional turrors had a higher two year survival rate than those with non-functional turrors (37.5% versus 24%). Since 1966, o-p 0 - DDD was used postoperatively as an adjuvant to surgery in 34 patients with a two year survival in this group of 32%. Surgery alone was used as treatment in 26/72 patients with a two year survival of 41%. Addition of Cytotoxic cherrotherapy or radiation therapy had little effect on two year survival with only 1/16 patients surviving longer than two years. These data suggests that the additional of o-p 0 DDD, radiation therapy, or cherrotherapy to extirpative surgery does little to alter the natural history of the disease.
'.l'l!E EFFECT OF HIGH ENERGY SHOCK WAVES ON CHINESE HAMSTER OVARY CELL. Chi-rei Yang*, Connie Bueti*, Robert Huryk*, Frank Traganos~ New York, N.Y. (Presentation to be made by Dr. Yang) The effect of high energy shock waves (HESW) on Chinese hamster ovary (CHO) cell viability and proliferation was investigated. Following l!ESW exposure of varying dosage, a dose dependent increase in cytotoxicity was observed; approximately 400 HESW reduced the viability of exponentially growing cells by 50%. The sensitivity of HES\'/ of exponentially growing and stationary phase CHO cells was comparable over the dose range of 0-600. The sensitivity of various cell cycle phases to HESW was determined following cell synchronization. Mitotic cells showed a marginally greater sensitivity to moderate levels of HESW with G1 , Sand G2 phase cells demonstrating equivalent sensitivity. Synchronized CHO cell populations were delayed in their traverse of the first cell cycle following treatment. However, by 12 hr (approximately equal to the duration of exponentially growing CHO cells) cell proliferation and clonogenicity returned to near normal values. Thus, the inunediate decrease in cell number and viability was the principle effects of HESW with the majority of surviving cells capable (after a delay) of reinitiating normal cell growth.
499
500
HIGH ENERGY SHOCK WAVES (HESW) INHIBIT TUMOR CELL PROLIFERATION AND POTENTIATE EFFICACY OF CYTOTOXIC AGENTS. Michael E. Berens*. Charles E. Welander*.
Andrew S.
TETRACYCLINE SCLEROTHERAPY OF HYDROCELES - NEED FOR IMPROVED TECHNIQUE. Sheldon F. Marks*, Grannum R. Sant, and Edwin M. Meares, Jr., Boston, MA:
Griffin* and David L. McCullough, Winston-Salem, NC; Wer-
by Dr. Marks).
ner Schwarze*. Gennering FRG.
(Presentation to be made by
(Presentation to be made
dependent inhibition of colony growth was found over the
Aspiration and tetracycline sclerotherapy treatment of hydroceles is an alternative to surgical repair. Seven patients, average age 50 years (range 24-75), were treated in the outpatient clinic. Pre-aspiration scrotal ultrasound examination was done in all patients to exclude testicular and epididymal abnormalities. Spermatic cord block and scrotal skin infiltration anesthesia was achieved with 0.5% Marcaine. Trans-scrotal aspiration was performed using a 1½ inch, 18 gauge angio cath. Aspirated
range of 400 to 2000 shocks. An endometrial cell line, HEC-1-A, was most sensitive (65% inhibition with 2000
fluid volume averaged 175 ml. (25-900 ml). Following aspiration, tetracycline (250 mg/ml) was injected into
shocks). and two ovarian lines. BG-1 and BG-3 1 demonstrated progressive inhibition with increasing doses (64%
the tunical sac. All patients experienced transient, mild post-operative discomfort. Follow-up has averaged 12 months, Three patients developed early recurrences (within two months). Successful repeat sclerotherapy was achieved in one patient and the others required surgical treatment. Our success rate of 57% is not as high as that reported in the literature. To ensure improved results, we suggest the following technical modifications to the technique - complete aspiration to ensure coaptation of the tunical layers, use of high tetracycline concentrations in low volumes, and scrotal compression for twenty-four hours post-operatively. With improved technique and patient selection, outpatient aspiration and tetracycline sclerotherapy should be a cost-effective, viable approach to the treatment of
Dr. McCullough) Human tumor cells were evaluated for changes in via-
bility. clonogenicity in soft agaroseii and sensitivity to chemotherapeutic agents after shock wave treatment. Shock
waves generated by an 18 kV discharge (HM-III, Dornier Medizintechnik) were without effect on cell number or viability determined by exclusion of trypan blue. Dose-
and 39% inhibition, respectively). Light shielding in opaque treatment tubes showed the same antiproliferative effect as treatment in unshielded tubes, ruling out the
possibility of UltraViolet light-induced cell damage.
The
poorly differentiated ovarian carcinoma line, BG-1. was tested for chemosensitivity against adriamycin, cytoxan or
cisplatin after treatment with 2000 HESW.
Cytoxan and
cisplatin were potentiated by nearly an order of magnitude, and adriamycin showed a 3-fold enhanced colony inhibition in shocked cellsG These results indicate that while HESW do not destroy cells outright, there is an antiproliferative effect of shock waves on human tumor
cells.
Additionally, cells pretreated with HESW become
markedly more sensitive to cytotoxic chemotherapy. The ability to deliver HESW to precise lo cat ions makes this an exciting prospect for development of regional hyperresponsive cancer therapy. [Supported by a grant from Dornier Medizintechnik,
hydroceles.
Germering, FRG.]
228A
498
ADRENAL CORTICAL CARCINOMA - THE CLEVELAND CLINIC EXPERIENCE. *Barry H. Bodie, Cleveland, OH (Presentation to be made by Dr. Bodie) . Between 1936 and 1986, seventy-two patients (35 males, 37 females) with histologically proven adrenal cortical carcinoma were seen at the Cleveland Clinic Foundation. Sixty-six of these patients were seen in the last 30 years. The average at presentation was 47 years (range 1.5 - 80 years). Four patients were children less than 18 years old. Thirty-six patients presented with a biochemically functional turror (9 males, 27 females), while the remainder had non-functioning turrors (26 males, 10 females). Metastatic disease was initially present in 41/72 patients (57%). Surgical extirpation of the turror was attempted in 60/72 patients. overall h.;o year survival in the series was 29% (31% in males, 29% in females). Patients with functional turrors had a higher two year survival rate than those with non-functional turrors (37.5% versus 24%). Since 1966, o-p 0 - DDD was used postoperatively as an adjuvant to surgery in 34 patients with a two year survival in this group of 32%. Surgery alone was used as treatment in 26/72 patients with a two year survival of 41%. Addition of Cytotoxic cherrotherapy or radiation therapy had little effect on two year survival with only 1/16 patients surviving longer than two years. These data suggests that the additional of o-p 0 DDD, radiation therapy, or cherrotherapy to extirpative surgery does little to alter the natural history of the disease.
'.l'l!E EFFECT OF HIGH ENERGY SHOCK WAVES ON CHINESE HAMSTER OVARY CELL. Chi-rei Yang*, Connie Bueti*, Robert Huryk*, Frank Traganos~ New York, N.Y. (Presentation to be made by Dr. Yang) The effect of high energy shock waves (HESW) on Chinese hamster ovary (CHO) cell viability and proliferation was investigated. Following l!ESW exposure of varying dosage, a dose dependent increase in cytotoxicity was observed; approximately 400 HESW reduced the viability of exponentially growing cells by 50%. The sensitivity of HES\'/ of exponentially growing and stationary phase CHO cells was comparable over the dose range of 0-600. The sensitivity of various cell cycle phases to HESW was determined following cell synchronization. Mitotic cells showed a marginally greater sensitivity to moderate levels of HESW with G1 , Sand G2 phase cells demonstrating equivalent sensitivity. Synchronized CHO cell populations were delayed in their traverse of the first cell cycle following treatment. However, by 12 hr (approximately equal to the duration of exponentially growing CHO cells) cell proliferation and clonogenicity returned to near normal values. Thus, the inunediate decrease in cell number and viability was the principle effects of HESW with the majority of surviving cells capable (after a delay) of reinitiating normal cell growth.
499
500
HIGH ENERGY SHOCK WAVES (HESW) INHIBIT TUMOR CELL PROLIFERATION AND POTENTIATE EFFICACY OF CYTOTOXIC AGENTS. Michael E. Berens*. Charles E. Welander*.
Andrew S.
TETRACYCLINE SCLEROTHERAPY OF HYDROCELES - NEED FOR IMPROVED TECHNIQUE. Sheldon F. Marks*, Grannum R. Sant, and Edwin M. Meares, Jr., Boston, MA:
Griffin* and David L. McCullough, Winston-Salem, NC; Wer-
by Dr. Marks).
ner Schwarze*. Gennering FRG.
(Presentation to be made by
(Presentation to be made
dependent inhibition of colony growth was found over the
Aspiration and tetracycline sclerotherapy treatment of hydroceles is an alternative to surgical repair. Seven patients, average age 50 years (range 24-75), were treated in the outpatient clinic. Pre-aspiration scrotal ultrasound examination was done in all patients to exclude testicular and epididymal abnormalities. Spermatic cord block and scrotal skin infiltration anesthesia was achieved with 0.5% Marcaine. Trans-scrotal aspiration was performed using a 1½ inch, 18 gauge angio cath. Aspirated
range of 400 to 2000 shocks. An endometrial cell line, HEC-1-A, was most sensitive (65% inhibition with 2000
fluid volume averaged 175 ml. (25-900 ml). Following aspiration, tetracycline (250 mg/ml) was injected into
shocks). and two ovarian lines. BG-1 and BG-3 1 demonstrated progressive inhibition with increasing doses (64%
the tunical sac. All patients experienced transient, mild post-operative discomfort. Follow-up has averaged 12 months, Three patients developed early recurrences (within two months). Successful repeat sclerotherapy was achieved in one patient and the others required surgical treatment. Our success rate of 57% is not as high as that reported in the literature. To ensure improved results, we suggest the following technical modifications to the technique - complete aspiration to ensure coaptation of the tunical layers, use of high tetracycline concentrations in low volumes, and scrotal compression for twenty-four hours post-operatively. With improved technique and patient selection, outpatient aspiration and tetracycline sclerotherapy should be a cost-effective, viable approach to the treatment of
Dr. McCullough) Human tumor cells were evaluated for changes in via-
bility. clonogenicity in soft agaroseii and sensitivity to chemotherapeutic agents after shock wave treatment. Shock
waves generated by an 18 kV discharge (HM-III, Dornier Medizintechnik) were without effect on cell number or viability determined by exclusion of trypan blue. Dose-
and 39% inhibition, respectively). Light shielding in opaque treatment tubes showed the same antiproliferative effect as treatment in unshielded tubes, ruling out the
possibility of UltraViolet light-induced cell damage.
The
poorly differentiated ovarian carcinoma line, BG-1. was tested for chemosensitivity against adriamycin, cytoxan or
cisplatin after treatment with 2000 HESW.
Cytoxan and
cisplatin were potentiated by nearly an order of magnitude, and adriamycin showed a 3-fold enhanced colony inhibition in shocked cellsG These results indicate that while HESW do not destroy cells outright, there is an antiproliferative effect of shock waves on human tumor
cells.
Additionally, cells pretreated with HESW become
markedly more sensitive to cytotoxic chemotherapy. The ability to deliver HESW to precise lo cat ions makes this an exciting prospect for development of regional hyperresponsive cancer therapy. [Supported by a grant from Dornier Medizintechnik,
hydroceles.
Germering, FRG.]
228A