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Chemosensitizing effect of an antiestrogen, toremifene, on ovarian cancer
326
Citations from the Literature
A cohort study of the risk of cervical intraepitkelial neoplasia grade 2 or 3 in relation to papillomaviros infection Koutsky LA; Holmes KK; Critchlow CW; Stevens CE; Paavonen J; Beckmann AM; DeRouen TA; Galloway DA; Vernon D, Kiviat NB AIDS/Sexually Transmitted Dis. Ctr., 1001 Broadway, Seattle, WA 98122, USA
NEW ENGL J MED 1992 327/18 (1272-1278) Background. Human papillomavirus (HPV) has been associated with cervical intraepithelial neoplasia, but the temporal relation between the infection and the neoplasia remains unclear, as does the relative importance of the specific type of HPV, other sexually transmitted diseases, and other risk factors. Methods. We studied prospectively a cohort of 241 women who presented for evaluation of sexually transmitted disease and had negative cervical cytologic tests. The women were followed every four months with cytologic and colposcopic examinations of the uterine cervix and tests for HPV DNA and other sexually transmitted diseases. Results. Cervical intraepithelial neoplasia grade 2 or 3 was confirmed by biopsy in 28 women. On the basis of survival analysis, the cumulative incidence of cervical intraepithelial neoplasia at two years was 28% among women with a positive test for HPV and 3% among those without detectable HPV DNA. The risk was highest among those with HPV type 16 or 18 infection (adjusted relative risk as compared with that in women without HPV infection, 11; 95% contidence interval, 4.6 to 26; attributable risk, 52%). All 24 cases of cervical intraepithelial neoplasia grade 2 or 3 among HPV-positive women were detected within 24 months after the first positive test for HPV. After adjustment for the presence of HPV infection, the development of cervical intraepithelial neoplasia was also associated with younger age at first intercourse, the presence of serum antibodies to Chlamydia trachomatis, the presence of serum antibodies to cytomegalovirus, and cervical infection with Neisseria gonorrhoeae. Conclusions. Cervical intraepithehal neoplasia is a common and apparently early manifestation of cervical infection by HPV, particularly types 16 and 18. The role of cytoreductivesurgery in the managementof Stage IV epithelial ovarian carcinoma Goodman HM; Harlow BL; Sheets EE; Muto MG; Brooks S; Steller M; Knapp RC; Berkowitz RS Dept. of Ob/GyniReproductive Biology, Harvard Medical School, Brigham and Women’s Hospital, Boston, MA 02115. USA
GYNECOL ONCOL 1992 46/3 (367-371) Patients with Stage IV epithehal ovarian carcinoma are generally treated in the same manner as are patients with disease confined to the abdomen-cytoreductive surgery followed by combination chemotherapy. Between 1980 and 1990, 35 women with histologically or cytologically documented Stage IV ovarian carcinoma were treated in this fashion. Sixteen women (45%) underwent optimal initial cytoreductive surgery, defined as less than 2 cm maximum residual disease. Eleven of the I9 women undergoing suboptimal initial procedures underwent interval cytoreduction after two to four cycles of chemoInt J Gynecol Obstet 41
therapy, with 7 achieving an optimal status after the interval procedure. Overall, 23 of 35 patients (66%) were successfully cytoreduced to less than 2 cm either initially or at an interval procedure. Thirty-one of the 35 patients received combination regimens containing platinum as part of their initial therapy. Kaplan-Meier survival curves demonstrated no significant difference in survival between those groups of women cytoreduced intervally or initially, or between those groups of women optimally cytoreduced at some point during their initial therapy and those who were not. The 5-year survival for the entire group was less than 5%, with no significantly prolonged survival seen in those patients undergoing successful cytoreduction. Chemoseasitiziageffect of an antiestrogen, toremifene, on ovarian caacer Maenpaa J; Sipila P; Kangas L; Kamani P; Gronroos M Department of Obstetrics/Gynecology, University Central Hospital of Turku, Turku. FIN
GYNECOL ONCOL 1992 46/3 (292-297) The chemosensitizing effect of an antiestrogen, toremifene, was studied on 2 human ovarian cancer cell lines in vitro and on 3 fresh surgical ovarian tumor explants with the aid of the subrenal capsule assay (SRCA). Also, I j patients with secondarily drug resistant, recurrent gynecologic cancer (8 ovarian and 3 uterine cancers) were treated with 240 mg toremifene daily for 1 week before each course of cytostatics. Toremifene potentiated the effect of doxorubicin on both cell lines. This was also the case on 1cell line that was not completely resistant to doxorubicin. The SRCA showed a clear potentiating effect of toremifene only on the tumor overtly resistant to the combination of cisplatin, doxorubicin, and cyclophosphamide. Of the I1 patients treated with toremifene and cytostatics, the response of 8 patients was evaluable: 3 had partial response, 3 no change, and 2 progressive disease. Toremifene seems to have a chemopotentiating effect on gynecologic drug-resistant tumors. Goaadotropb, eatradiol, aad growth factors regulate epithelial ovariaa caacer cell growth Wimalasena J; Dostal R; Meehan D Dept. of OB/G YN, University of Tennessee Medical Ctr., 1924 Alcoa Highway, Knoxville, TN 37920-6999, USA
GYNECOL ONCOL 1992 4613 (345-350) Indirect evidence suggests that gonadal steroids and gonadotropins may have a role in the genesis of epithelial ovarian cancer. In the studies reported herein, we established 17& estradiol (E2) secreting cell cultures from an omental metastasis of an epithelial ovarian cancer. We demonstrate that human chorionic gonadotropin (hCG), human folliclestimulating hormone, and epidermal growth factor (EGF) increased cell growth in a dose- and time-dependent manner, whereas Ez inhibited cell growth in the nanomolar rnge. Epidermal growth factor was able to partially block the negative effect of E,; a similar but quantitatively lesser effect was observed with hCG. These results provide direct evidence to support the view that gonadotropins, EGF, TGFfl (transforming growth factor), and estradiol may modulate growth of metastatic epithelial ovarian cancer cells,
Citations from the Literature
A cohort study of the risk of cervical intraepitkelial neoplasia grade 2 or 3 in relation to papillomaviros infection Koutsky LA; Holmes KK; Critchlow CW; Stevens CE; Paavonen J; Beckmann AM; DeRouen TA; Galloway DA; Vernon D, Kiviat NB AIDS/Sexually Transmitted Dis. Ctr., 1001 Broadway, Seattle, WA 98122, USA
NEW ENGL J MED 1992 327/18 (1272-1278) Background. Human papillomavirus (HPV) has been associated with cervical intraepithelial neoplasia, but the temporal relation between the infection and the neoplasia remains unclear, as does the relative importance of the specific type of HPV, other sexually transmitted diseases, and other risk factors. Methods. We studied prospectively a cohort of 241 women who presented for evaluation of sexually transmitted disease and had negative cervical cytologic tests. The women were followed every four months with cytologic and colposcopic examinations of the uterine cervix and tests for HPV DNA and other sexually transmitted diseases. Results. Cervical intraepithelial neoplasia grade 2 or 3 was confirmed by biopsy in 28 women. On the basis of survival analysis, the cumulative incidence of cervical intraepithelial neoplasia at two years was 28% among women with a positive test for HPV and 3% among those without detectable HPV DNA. The risk was highest among those with HPV type 16 or 18 infection (adjusted relative risk as compared with that in women without HPV infection, 11; 95% contidence interval, 4.6 to 26; attributable risk, 52%). All 24 cases of cervical intraepithelial neoplasia grade 2 or 3 among HPV-positive women were detected within 24 months after the first positive test for HPV. After adjustment for the presence of HPV infection, the development of cervical intraepithelial neoplasia was also associated with younger age at first intercourse, the presence of serum antibodies to Chlamydia trachomatis, the presence of serum antibodies to cytomegalovirus, and cervical infection with Neisseria gonorrhoeae. Conclusions. Cervical intraepithehal neoplasia is a common and apparently early manifestation of cervical infection by HPV, particularly types 16 and 18. The role of cytoreductivesurgery in the managementof Stage IV epithelial ovarian carcinoma Goodman HM; Harlow BL; Sheets EE; Muto MG; Brooks S; Steller M; Knapp RC; Berkowitz RS Dept. of Ob/GyniReproductive Biology, Harvard Medical School, Brigham and Women’s Hospital, Boston, MA 02115. USA
GYNECOL ONCOL 1992 46/3 (367-371) Patients with Stage IV epithehal ovarian carcinoma are generally treated in the same manner as are patients with disease confined to the abdomen-cytoreductive surgery followed by combination chemotherapy. Between 1980 and 1990, 35 women with histologically or cytologically documented Stage IV ovarian carcinoma were treated in this fashion. Sixteen women (45%) underwent optimal initial cytoreductive surgery, defined as less than 2 cm maximum residual disease. Eleven of the I9 women undergoing suboptimal initial procedures underwent interval cytoreduction after two to four cycles of chemoInt J Gynecol Obstet 41
therapy, with 7 achieving an optimal status after the interval procedure. Overall, 23 of 35 patients (66%) were successfully cytoreduced to less than 2 cm either initially or at an interval procedure. Thirty-one of the 35 patients received combination regimens containing platinum as part of their initial therapy. Kaplan-Meier survival curves demonstrated no significant difference in survival between those groups of women cytoreduced intervally or initially, or between those groups of women optimally cytoreduced at some point during their initial therapy and those who were not. The 5-year survival for the entire group was less than 5%, with no significantly prolonged survival seen in those patients undergoing successful cytoreduction. Chemoseasitiziageffect of an antiestrogen, toremifene, on ovarian caacer Maenpaa J; Sipila P; Kangas L; Kamani P; Gronroos M Department of Obstetrics/Gynecology, University Central Hospital of Turku, Turku. FIN
GYNECOL ONCOL 1992 46/3 (292-297) The chemosensitizing effect of an antiestrogen, toremifene, was studied on 2 human ovarian cancer cell lines in vitro and on 3 fresh surgical ovarian tumor explants with the aid of the subrenal capsule assay (SRCA). Also, I j patients with secondarily drug resistant, recurrent gynecologic cancer (8 ovarian and 3 uterine cancers) were treated with 240 mg toremifene daily for 1 week before each course of cytostatics. Toremifene potentiated the effect of doxorubicin on both cell lines. This was also the case on 1cell line that was not completely resistant to doxorubicin. The SRCA showed a clear potentiating effect of toremifene only on the tumor overtly resistant to the combination of cisplatin, doxorubicin, and cyclophosphamide. Of the I1 patients treated with toremifene and cytostatics, the response of 8 patients was evaluable: 3 had partial response, 3 no change, and 2 progressive disease. Toremifene seems to have a chemopotentiating effect on gynecologic drug-resistant tumors. Goaadotropb, eatradiol, aad growth factors regulate epithelial ovariaa caacer cell growth Wimalasena J; Dostal R; Meehan D Dept. of OB/G YN, University of Tennessee Medical Ctr., 1924 Alcoa Highway, Knoxville, TN 37920-6999, USA
GYNECOL ONCOL 1992 4613 (345-350) Indirect evidence suggests that gonadal steroids and gonadotropins may have a role in the genesis of epithelial ovarian cancer. In the studies reported herein, we established 17& estradiol (E2) secreting cell cultures from an omental metastasis of an epithelial ovarian cancer. We demonstrate that human chorionic gonadotropin (hCG), human folliclestimulating hormone, and epidermal growth factor (EGF) increased cell growth in a dose- and time-dependent manner, whereas Ez inhibited cell growth in the nanomolar rnge. Epidermal growth factor was able to partially block the negative effect of E,; a similar but quantitatively lesser effect was observed with hCG. These results provide direct evidence to support the view that gonadotropins, EGF, TGFfl (transforming growth factor), and estradiol may modulate growth of metastatic epithelial ovarian cancer cells,