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Calcium channel blockers (CCBs) decrease chemotaxis in ovarian cancer cells
412
SOCIETY
OF GYNECOLOGIC
ONCOLOGISTS-ABSTRACTS
containing serous or clear cell carcinoma, and deep invasion and LNM much more often MMT consisted of carcinoma alone (20 cases) than sarcoma alone (4 cases). Progression-free interval and survival up to 2 years have thus far correlated only with LNM, I or C location, and LVSI. 16. Metastatic Gestational Trophohlastic Disease: Experience at the New England Trophoblustic Disease Centerfrom 1965 to 1985. B. DUBESHTER, R. S. BERKOWITZ, D. P. GOLDSTEIN, D. CRAMER, AND M. BERNSTEIN, Brigham & Women’s Hospital, Department of Obstetrics & Gynecology, Harvard Medical School, Boston, Massachusetts 02115. The current study reviews the results of therapy in 93 patients with metastatic gestational trophoblastic tumors between 1965 and 1985. Complete remission was achieved in 42 patients with low-risk metastatic disease and in 34 of 51 (67%) patients with high-risk metastatic disease. Single-agent chemotherapy induced complete remission in 38 of 42 (91%) patients with low-risk metastatic disease. There was a marked improvement in survival of high-risk patients over the past two decades. Complete remission was attained in 13 of 24 (54%) high-risk patients between 1965 and 1975 and in 21 of 27 (78%) high-risk patients between 1976 and 1985. Survival was correlated with the number of high-risk factors, the prognostic score, and the type of treatment employed. Between 1965 and 1975 54% (13/24) of high-risk patients were treated with single-agent chemotherapy alone while in the last decade only 7% (2/27) were treated in this fashion. Twenty-one patients with traditional high-risk factors had a prognostic score <8 and all achieved remission, with 67% being treated with primary single-agent therapy. While all patients with prognostic score <8 survived, the survival rate progressively declined as the prognostic score increased above 8. The prognostic scoring system as compared to traditional high-risk criteria was more predictive of which patients require intensive combination chemotherapy to attain remission. 17. Calcium Chunnel Blockers (CCBs) Decrease Chemotaxis in Ovariun Cancer Cells. G. M. BOIKE, K. V. HONN, B. F. SLOAN. J. M. ONODA, J. THOMPSON, V. K. MALVIYA, AND G. DEPPE. Wayne State University, Detroit, Michigan 48201. The intraperitoneal spread of ovarian cancer occurs as a result of exfoliation and peritoneal fluid dynamics. The role of directed migration or chemotaxis and attempts to modulate this process have received little attention. Honn et al. (Proc. Sot. Exp. Biol. Med. 174, 16 (1983)) have shown that the CCB, nifedipine inhibited tumor cell-induced platelet aggregation and experimental metastases in two different animal models, while Elferink et al. (Biochem. Pharmacol. 33, 35 (1984)) have shown that several CCBs are capable of decreasing chemotaxis in rabbit neutrophils. Using a human ovarian cancer cell line, Ov-J, we studied the response to autocrine motility factor (AMF; Proc. Nat/. Acud. Sci. USA 83, 3302 (1986)) in the presence and absence of several different CCBs. Chemotaxis assays were performed using Boyden chambers and filters precoated with basement membrane collagen. The CCBs used were diltiazem. nifedipine, and verapamil, at 50 and 500 PM. Experimental results were compared to the positive control (AMF alone) using a one-way ANOVA, and a P < 0.05 was considered significant. All of the CCBs tested caused a statistically significant reduction in chemotaxis between 5 and 30% of control at the 500 FM concentration, but not at the 50 WM concentration. Differences in potency between agents were not statistically significant. Under experimental conditions, tumor cell viability was unaffected as determined by trypan blue dye exclusion. It appears that CCBs are effective in decreasing chemotaxis in ovarian cancer cells. Agents capable of modulating calcium homeostasis should be further studied for their ability to interfere with processes known to be important in tumor cell invasion and metastases. 18. DNA Ploidy in Ovarian Cancer. P. BRALY AND D. BLUMENFELD, Center, Duarte, California 91010.
City of Hope National
Medical
Eighty-three patients with advanced epithelial ovarian carcinoma were evaluated in a retrospective study to determine the prognostic value of tumor cellular DNA content (ploidy) in ovarian carcinoma. A total of 251 DNA histograms were anlayzed using flow cytometry (FCM) from paraffin-embedded specimens. Cox regression analysis revealed that age (P < O.OOl), stage (P < O.OOl), and ploidy (P < 0.001) were the independent prognostic features in predicting the outcome of these patients. The
SOCIETY
OF GYNECOLOGIC
ONCOLOGISTS-ABSTRACTS
containing serous or clear cell carcinoma, and deep invasion and LNM much more often MMT consisted of carcinoma alone (20 cases) than sarcoma alone (4 cases). Progression-free interval and survival up to 2 years have thus far correlated only with LNM, I or C location, and LVSI. 16. Metastatic Gestational Trophohlastic Disease: Experience at the New England Trophoblustic Disease Centerfrom 1965 to 1985. B. DUBESHTER, R. S. BERKOWITZ, D. P. GOLDSTEIN, D. CRAMER, AND M. BERNSTEIN, Brigham & Women’s Hospital, Department of Obstetrics & Gynecology, Harvard Medical School, Boston, Massachusetts 02115. The current study reviews the results of therapy in 93 patients with metastatic gestational trophoblastic tumors between 1965 and 1985. Complete remission was achieved in 42 patients with low-risk metastatic disease and in 34 of 51 (67%) patients with high-risk metastatic disease. Single-agent chemotherapy induced complete remission in 38 of 42 (91%) patients with low-risk metastatic disease. There was a marked improvement in survival of high-risk patients over the past two decades. Complete remission was attained in 13 of 24 (54%) high-risk patients between 1965 and 1975 and in 21 of 27 (78%) high-risk patients between 1976 and 1985. Survival was correlated with the number of high-risk factors, the prognostic score, and the type of treatment employed. Between 1965 and 1975 54% (13/24) of high-risk patients were treated with single-agent chemotherapy alone while in the last decade only 7% (2/27) were treated in this fashion. Twenty-one patients with traditional high-risk factors had a prognostic score <8 and all achieved remission, with 67% being treated with primary single-agent therapy. While all patients with prognostic score <8 survived, the survival rate progressively declined as the prognostic score increased above 8. The prognostic scoring system as compared to traditional high-risk criteria was more predictive of which patients require intensive combination chemotherapy to attain remission. 17. Calcium Chunnel Blockers (CCBs) Decrease Chemotaxis in Ovariun Cancer Cells. G. M. BOIKE, K. V. HONN, B. F. SLOAN. J. M. ONODA, J. THOMPSON, V. K. MALVIYA, AND G. DEPPE. Wayne State University, Detroit, Michigan 48201. The intraperitoneal spread of ovarian cancer occurs as a result of exfoliation and peritoneal fluid dynamics. The role of directed migration or chemotaxis and attempts to modulate this process have received little attention. Honn et al. (Proc. Sot. Exp. Biol. Med. 174, 16 (1983)) have shown that the CCB, nifedipine inhibited tumor cell-induced platelet aggregation and experimental metastases in two different animal models, while Elferink et al. (Biochem. Pharmacol. 33, 35 (1984)) have shown that several CCBs are capable of decreasing chemotaxis in rabbit neutrophils. Using a human ovarian cancer cell line, Ov-J, we studied the response to autocrine motility factor (AMF; Proc. Nat/. Acud. Sci. USA 83, 3302 (1986)) in the presence and absence of several different CCBs. Chemotaxis assays were performed using Boyden chambers and filters precoated with basement membrane collagen. The CCBs used were diltiazem. nifedipine, and verapamil, at 50 and 500 PM. Experimental results were compared to the positive control (AMF alone) using a one-way ANOVA, and a P < 0.05 was considered significant. All of the CCBs tested caused a statistically significant reduction in chemotaxis between 5 and 30% of control at the 500 FM concentration, but not at the 50 WM concentration. Differences in potency between agents were not statistically significant. Under experimental conditions, tumor cell viability was unaffected as determined by trypan blue dye exclusion. It appears that CCBs are effective in decreasing chemotaxis in ovarian cancer cells. Agents capable of modulating calcium homeostasis should be further studied for their ability to interfere with processes known to be important in tumor cell invasion and metastases. 18. DNA Ploidy in Ovarian Cancer. P. BRALY AND D. BLUMENFELD, Center, Duarte, California 91010.
City of Hope National
Medical
Eighty-three patients with advanced epithelial ovarian carcinoma were evaluated in a retrospective study to determine the prognostic value of tumor cellular DNA content (ploidy) in ovarian carcinoma. A total of 251 DNA histograms were anlayzed using flow cytometry (FCM) from paraffin-embedded specimens. Cox regression analysis revealed that age (P < O.OOl), stage (P < O.OOl), and ploidy (P < 0.001) were the independent prognostic features in predicting the outcome of these patients. The