Assessment of soluble intracellular adhesion molecule-1 (sICAM-1) in women with benign ovarian tumors

OBJECTIVES: Overexpression of intracellular adhesion molecule-I (ICAM-1) was observed in many benign and malignant tumors. The aim of our study was to evaluate its serum concentrations as well as CA-125 in women with benign ovarian tumors. MATERIALS AND METHODS: Forty-five women treated surgically because of benign ovarian mass. RESULTS: Mean concentrations of sICAM-1 in benign tumors was 241.8+/-74.1 ng/ml and 195.6+/-68.7 ng/ml in healthy controls. No correlations between sICAM-1 concentrations and leukocyte count, tumor volume, BMI and obstetrical history. Efficiency in tumor differentiation was higher for CA-125 than sICAM-1 (area under Receiver Operating Characteristic curve 0.78 and 0.63 respectively). We observed higher sICAM-1 concentrations in fibrothecomas and lower in endometrial and dermoid cysts. CONCLUSIONS: Serum ICAM-1 concentrations correlate with some histological types of benign tumors, but not with tumor volume. Levels of CA-125 are more effective than ICAM-1 in ovarian tumors differentiation.     

Antitumor effect of GnRH agonist in epithelial ovarian cancer.

OBJECTIVE: The effects of the gonadotropin releasing hormone (GnRH) agonist (D-Trp(6)) were examined in two human ovarian cancer cell lines and in severe combined immune deficiency (SCID) mice to evaluate its potential as a cytocidal, cytostatic, or differentiating antitumor agent. METHODS: We treated the human ovarian cancer cell lines OVCAR-3 and SKOV-3 for 5 or 7 days and sex-matched SCID mice with GnRH agonist for 29 days. The antitumor effect of GnRH agonist were studied in various aspects. To confirm the antiproliferative effect, we used 3-(4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide colorimetric assay, in vitro, and a serial measurement of tumor growth in vivo. The disturbances of progression in the cell cycle and the changes of cyclin-dependent kinase 1 following treatment with GnRH agonist were evaluated with flow cytometric analysis in vitro. The induction of apoptosis following treatment with GnRH agonist was studied using in situ terminal deoxyribonucleotidyl transferase (Tdt) and further quantitated with ELISA in vitro. The presence of telomerase activity following treatment with GnRH agonist was measured by PCR-based telomeric repeat amplification protocol and ELISA detection in cell lines and xenografts in vitro and in vivo. RESULTS: Continuous exposure of cell lines and xenografts to GnRH agonist resulted in growth inhibition of cancer cells in a dose- and time-dependent manner. In cultured cells, the GnRH agonist blocked cell cycle progression in G0/G1 phase and thus reduced the number of cells in S and G2/M phases. The phenomenon of apoptosis was documented in cultured cells treated with GnRH agonist by in situ Tdt assay. The frequency of apoptotic cells in the in situ Tdt assay was 5-6% compared with control, 4-5%. Apoptosis quantified by ELISA revealed a high incidence in cultured cells treated with GnRH agonist. The activities of telomerase in cell lines and xenografts were not decreased by GnRH agonist. There were not any significant changes of expression of CA-125 by flow cytometry and of the cellular morphology observed with light microscopy. CONCLUSIONS: Our results indicate that the antiproliferative effect of GnRH agonist in epithelial ovarian cancer cells may be mainly attributed to cytostatic activities resulting in blocking of cell cycle progression in the G0/G1 phase and minimally related to the induction of apoptosis.     

Lower levels of inhibin A and pro-alphaC during the luteal phase after triggering oocyte maturation with a gonadotropin-releasing hormone agonist versus human chorionic gonadotropin

OBJECTIVE: To investigate the effect of triggering oocyte maturation with GnRH agonist on corpus luteum function by measuring luteal phase levels of inhibin A and pro-alphaC. DESIGN: Prospective randomized trial. SETTING: In vitro fertilization (IVF) program at a university hospital. PATIENT(S): Infertile women undergoing IVF-ET treatment. INTERVENTION(S): Controlled ovarian hyperstimulation with FSH and GnRH antagonist, triggering of final oocyte maturation with either hCG (n = 8) or GnRH agonist (n = 8), IVF-ET, and collection of blood samples every 2-3 days during the luteal phase. MEASUREMENTS AND MAIN RESULTS: Luteal phase serum levels of inhibin A and pro-alphaC, P, and E(2). RESULT(S): Levels of inhibin A, pro-alphaC, estrogen, and P were significantly lower from day 4 to day 14 after triggering final oocyte maturation by GnRH agonist compared with hCG. Maximal luteal serum inhibin A and pro-alphaC levels were 91.5 +/- 23.6 and 184.1 +/- 23.5 pg/mL in the GnRH agonist-treated women compared with 464.7 +/- 209.1 and 7,351.6 +/- 934.3 pg/mL in women treated with hCG. CONCLUSION(S): Triggering final oocyte maturation with GnRH agonist instead of hCG in IVF cycles dramatically decreases luteal levels of inhibins, reflecting significant inhibition of the corpus luteum function. This effect may explain, at least in part, the mechanism of ovarian hyperstimulation syndrome prevention by the use of GnRH agonist.     

bFGF单克隆抗体对卵巢癌移植瘤血管生成的抑制作用

目的:探讨碱性成纤维细胞生长因子(bFGF)在卵巢上皮性肿瘤中的表达强度与肿瘤血管生成之间的关系,及其单克隆抗体bFGFMAb对人卵巢癌移植瘤血管生成和肿瘤生长的影响。方法:(1)应用免疫组化法和图像分析系统研究bFGF在正常卵巢组织,良性、交界性和恶性卵巢上皮性肿瘤中的表达部位和强度;以及bFGF的表达强度与肿瘤新生血管的关系;(2)利用卵巢癌裸鼠皮下移植瘤模型,每周2次将不同浓度的bFGFMAb注射于瘤体周围,连续8周,每周测量肿瘤体积,绘制移植瘤生长曲线;对移植瘤组织行Ⅷ因子的免疫组化染色,测定肿瘤内微血管密度(MVD)。结果:(1)bFGF主要在卵巢上皮性肿瘤细胞浆内表达,在交界性和恶性肿瘤中,部分细胞同时存在核表达;bFGF在正常卵巢组织,良性、交界性和恶性卵巢上皮性肿瘤中的表达强度逐步增强,同时MVD逐步增高,二者呈正相关(P<0.001);(2)30、20、10μgbFGFMAb组移植瘤体积分别是对照组的31.34%、49.20%和71.25%,MVD分别是对照组的27.80%、52.37%和81.86%(P<0.05),其作用呈浓度依赖性。结论:bFGFMAb能明显抑制卵巢癌的血管生成和肿瘤生长,有望成为卵巢癌生物治疗的新方法。     

GnRH antagonist in the adjuvant treatment of a recurrent ovarian granulosa cell tumor: a case report

BACKGROUND: Ovarian granulosa cell tumors (GCT) are usually treated by surgery and chemotherapy. Successful response to GnRH agonists as an adjuvant therapy has previously been reported. In this case of recurrent GCT, we used a GnRH antagonist. CASE: A 78-year-old woman underwent surgery for an ovarian granulosa cell tumor (pT1a N0 Mx). Six months later, laparotomy revealed an inoperable recurrence of the tumor. Experimental treatment with a GnRH antagonist was not clearly successful. This is in contrast to the previously proven benefit of GnRH agonist therapy in this type of malignancy and to the positive response elicited by GnRH antagonists in epithelial ovarian tumors. CONCLUSION: GnRH antagonist therapy had no demonstrable efficacy in the treatment of a poorly differentiated and aggressive recurrent granulosa cell tumor.     

Follicular fluid vascular endothelial growth factor concentrations are increased during GnRH antagonist/FSH ovarian stimulation cycles

BACKGROUND: The aim of this study was to investigate the effect of GnRH antagonists (GnRH-ant) on follicular fluid vascular endothelial growth factor (FF VEGF). METHODS: Sixty women undergoing assisted reproduction were randomised (computer-generated randomisation list) and assigned to two different GnRH analogue regimens: GnRH agonist (GnRH-a) (Group A; n = 30) and GnRH-ant (Group B; n = 30). RESULTS: Mean (+/-S.D.) FF VEGF concentrations were 1598+/-612 pg/mL and 2906+/-1558 pg/mL for Groups A and B, respectively (p < 0.001). In the women treated with GnRH-ant, we found a statistically significant reduction in serum LH levels (1.72+/-0.74 IU/L in Group A versus 0.93+/-0.43 IU/L in Group B, p < 0.001), in serum oestradiol (E2) levels (1562.1+/-410.7 pg/mL in Group A versus 1214.67+/-779.9 pg/mL in Group B, p < 0.05), in FF E2 levels (1146+/-593 ng/mL in Group A versus 621+/-435 ng/mL in Group B, p < 0.05), and in FF androstenedione levels (136+/-55 ng/mL in Group A versus 78+/-31 ng/mL in Group B, p < 0.001), as well as a reduction in the number of pregnancies, though not statistically significant (23.3% in Group A versus 16.6% in Group B). CONCLUSION: The increase in FF VEGF levels in women treated with GnRH-ant might be explained by a suppression of LH and E2 levels.     

RNAi介导的WFDC2基因沉默抑制人卵巢浆液性上皮癌生长的体内实验

目的:利用前期已构建WFDC2基因稳定低表达的人浆液性卵巢癌细胞株SKOV3,构建裸鼠皮下移植瘤模型,观察肿瘤生长、转移特点的变化。方法:选择前期构建的稳定株进行体内实验。分组:未处理肿瘤细胞组(OEC组)、转染慢病毒空载体组(OEC-mock组)和转染WFDC2小干扰RNA组(OEC-WFDC2-si组)。组织块移植法建立二代卵巢癌荷瘤裸鼠模型。绘制各组的肿瘤生长曲线,实验终点时比较各组肿瘤的体积和重量,免疫组化检测细胞核增殖抗原(PCNA)表达。结果:OEC-WFDC2-si组皮下移植瘤的生长速度显著慢于OEC组和OEC-mock组,差异有统计学意义(P0.05)。OECWFDC2-si组首次出现可见肿瘤的时间晚于OEC组和OEC-mock组,差异有统计学意义(P0.05)。移植后第23天,OEC-WFDC2-si组的肿瘤重量、体积和细胞核增殖抗原(PCNA)表达均低于对照组,差异有统计学意义(P0.05)。实验组和对照组均未发现淋巴结转移。结论:WFDC2基因沉默显著抑制人卵巢癌SKOV3细胞株在裸鼠体内的生长,WFDC2基因可能在人卵巢浆液性上皮癌进展中起重要作用。     

Secretory leukocyte protease inhibitor in ovarian endometriomas following GnRH agonist therapy

OBJECTIVE: To determine whether expression of secretory leukocyte protease inhibitor is affected in tissue and peritoneal fluid of women with ovarian endometriomas treated with GnRH analogues. METHODS: In 32 women with endometriomas (17 untreated and 15 treated with GnRH analogue) and 21 with ovarian cystadenomas, we examined the expression of secretory leukocyte protease inhibitor messenger RNA (mRNA) by Northern blot analysis; protein distribution was measured immunohistochemically. Concentrations of secretory leukocyte protease inhibitor in peritoneal fluid were measured by enzyme-linked immunosorbent assay. Expression of secretory leukocyte protease inhibitor in endometrioma explants in vitro was also studied with and without the GnRH analogue treatment. RESULTS: Secretory leukocyte protease inhibitor mRNA expression was identified only in untreated endometriomas. In the GnRH agonist-treated endometriomas, the semiquantitative H-score for secretory leukocyte protease inhibitor immunostaining was significantly lower than that for untreated endometriomas (P <.001). The peritoneal fluid of the GnRH agonist-treated women also contained significantly lower concentrations of secretory leukocyte protease inhibitor (median 76 ng/mL, interquartile range 51-131 ng/mL; P <.001) than untreated women (124 ng/mL, 70-186 ng/mL). Secretory leukocyte protease inhibitor in endometrioma explants in vitro was significantly inhibited by the GnRH analogue (P <.05). CONCLUSION: Expression of secretory leukocyte protease inhibitor in tissue and peritoneal fluid of women with ovarian endometriomas was decreased by GnRH agonist treatment.     

GnRH-agonist therapy in women with the polycystic ovarian syndrome: effects on ovarian volume and on gonadotropin and sex steroid levels

Eleven patients with infertility and polycystic ovarian syndrome were treated with the GnRH agonist buserelin, 100 micrograms administered intranasally 6 times daily. The ovarian volume and morphology were monitored by vaginal sonography, and serum levels of hormones were measured by immunoassay. The mean ovarian volume was reduced from 13.0 +/- 4.1 cm3 to 9.1 +/- 3.1 cm3 after 42 days of treatment, p less than 0.001. The number of discernible ovarian microcysts was reduced from 11.9 +/- 2.1 to 9.6 +/- 2.9, p less than 0.05. The gonadotropin levels were reduced in all patients; however, there was no direct relationship between the reduction in ovarian volume loss and the concomitant decrease in LH or FSH levels. The levels of testosterone and androstenedione were normalized, whilst estradiol was suppressed to postmenopausal levels during the treatment period. The decrease in ovarian volume and the suppressed levels of ovarian steroids therefore seem to be related to the inhibition of the pituitary-ovarian axis with the GnRH agonist.     

Gonadotropin and inhibin concentrations in early pregnancy in women with and without corpora lutea.

We compared serum concentrations of immunoreactive inhibin, hCG, and FSH in normal women with those of two groups of women lacking endogenous luteal function. Twelve functionally agonadal, hypergonadotropic women with premature ovarian failure were given replacement ovarian steroids. Donor oocytes were fertilized in vitro with the husband's semen, and embryos were transferred into these women. A second group of 12 women were normogonadotropic but anovulatory, had undergone previously unsuccessful in vitro fertilization, and possessed cryopreserved embryos. These women were suppressed with a GnRH agonist before sex hormone replacement. Serum samples collected at weeks 2, 3, 4-6, 8-10, and 12-14 of pregnancy were measured for FSH, hCG, and immunoreactive inhibin. Data were compared with concentrations in normally ovulating women with well-established dates of conception. Sex steroid replacement hormone levels did not differ between the ovarian-failure and agonist-suppressed women and approximated that of normal cycles until pregnancy; thereafter, estradiol and progesterone levels remained higher than normal. Despite excessive steroid replacement, FSH remained higher in women with ovarian failure than in agonist-suppressed or normal women. On immunoassay, inhibin failed to show an early rise at 4-6 weeks of pregnancy in either group of aluteal women (0.52 +/- 0.05 ng/mL), whereas normal women demonstrated 0.9 +/- 0.05 ng/mL inhibin in their sera (P less than .001). By 8-10 weeks of pregnancy, women with ovarian failure demonstrated inhibin concentrations identical to those of normal women (1.2 +/- 0.1 and 1.2 +/- 0.15 ng/mL, respectively), whereas agonist-suppressed women lagged behind (0.7 +/- 0.1 ng/mL) (P less than .02).(ABSTRACT TRUNCATED AT 250 WORDS)     

A clinically relevant orthotopic implantation nude mouse model of human epithelial ovarian cancer—based on consecutive observation

The aim of this study is to establish an orthotopic implantation nude mouse model of epithelial ovarian cancer (EOC) and observe its biologic features. A human ovarian tumor line SKOV3ipl previously grown subcutaneously was implanted orthotopically as intact tissue into the ovarian capsule of 64 nude mice. Every week eight mice were taken randomly, and the tumor growth pattern and extent of metastatic disease were monitored continuously. Those mice that died of disease were necropsied and the end date was recorded. The orthotopic implanted tumors demonstrated a 100% take rate. Three weeks after implantation the tumors grew fast and weighed 1149 +/- 152 mg, and 5 weeks after implantation the tumors reached a flat stage. The tumors metastasized more often to peritoneum (32/56) and diaphragm (18/56), then to pelvic lymph nodes (11/56) and lung (10/56), and then to the seldom invaded organs including the pancreas, the liver, the contralateral ovary, and the para-aortic lymph node. Eight nude mice became exhausted 7 weeks after implantation and died within 68 days after implantation. Our study, utilizing the SKOV3ipl cell, is the first model of consecutive observation of the process of invasion and metastasis of EOC. It should be useful in understanding the molecular biology of EOC and in the development of therapeutic modalities against metastasis.     

胞嘧啶脱氨酶基因联合5-氟胞嘧啶对卵巢癌裸鼠移植瘤的抑制作用

目的　了解胞嘧啶脱氨酶 (CD)基因联合 5 氟胞嘧啶 (5 FC)对卵巢癌裸鼠皮下移植瘤生长的抑制作用。方法　应用胚肾 2 93细胞扩增整合有CD基因的复制缺陷的腺病毒 ,并将其分离、提纯。以卵巢癌裸鼠模型作为研究对象。实验组 (5只 ) :将整合有CD基因的复制缺陷的腺病毒 0 1ml[1×10 10 菌斑形成单位 (pfu) /ml]注入瘤体内 ,隔日 1次 ,共 3次 ;同时将 5 FC按每次 4 0 0mg/kg注入裸鼠腹腔内 ,每日 2次 ,共 7d。对照组 (5只 ) :以同样方法将同体积生理盐水注入裸鼠体内。观察两组裸鼠的肿瘤生长速度及倍增时间。结果　 (1)整合有CD基因的腺病毒滴度为 1 0 7× 10 10 pfu/ml。 (2 )实验组裸鼠肿瘤生长明显受抑制 ,肿瘤体积由 9mm3 增加到 85 5mm3 ,而对照组肿瘤体积由 7mm3 增加到 2 0 14mm3 ,两组比较 ,差异有显著性 (P <0 0 5 ) ,这种显著性差异在用药结束后约 2 0d才表现出来 ,并维持约 30d。(3)实验组与对照组肿瘤倍增时间分别为 (8 1± 0 7)d和 (6 4± 0 7)d ,两组比较 ,差异有显著性 (P<0 0 5 )。结论　应用CD基因联合 5 FC对卵巢癌裸鼠移植瘤具有良好的抑制作用     

Premenstrual administration of gonadotropin-releasing hormone antagonist coordinates early antral follicle sizes and sets up the basis for an innovative concept of controlled ovarian hyperstimulation

OBJECTIVE: To investigate whether premenstrual administration of a GnRH antagonist coordinates early antral follicle sizes during the subsequent follicular phase. DESIGN: Prospective, longitudinal study. SETTING: University Hospital in France PATIENT(S): Twenty-five women, 50 cycles. INTERVENTION(S): On cycle day 2 (control/day 2), women underwent measurements of early antral follicles by ultrasound and serum FSH and ovarian hormones. On day 25, they received a single cetrorelix acetate administration, 3 mg. On the subsequent day 2 (premenstrual GnRH antagonist/day 2), participants were re-evaluated as on control/day 2. MAIN OUTCOME MEASURE(S): Magnitude of follicular size discrepancies. RESULT(S): Follicular diameters (4.1 +/- 0.9 vs. 5.5 +/- 1.0 mm) and follicle-to-follicle size differences decreased on premenstrual GnRH antagonist/day 2 as compared with control/day 2. Consistently, FSH (4.5 +/- 1.9 vs. 6.7 +/- 2.4 mIU/mL), E(2) (23 +/- 13 vs. 46 +/- 26 pg/mL), and inhibin B (52 +/- 30 vs. 76 +/- 33 pg/mL) were lower on GnRH antagonist/day 2 than on control/day 2. CONCLUSION(S): Premenstrual GnRH antagonist administration reduces diameters and size disparities of early antral follicles on day 2, likely through the prevention of luteal FSH elevation and early follicular development. This simple, original approach may be used to coordinate multifollicular development in controlled ovarian hyperstimulation.     

Circulating leptin levels during ovulation induction: relation to adiposity and ovarian morphology

OBJECTIVE: To assess serum leptin levels based on body habitus and ovarian morphology during controlled ovarian hyperstimulation. Design: Prospective analysis. SETTING: University IVF program. PATIENT(s): Women undergoing IVF-ET were divided into two groups, obese ovulatory women (n = 6; mean (+/-SD) body mass index, 30.1 +/- 0.6 kg/m(2)) and lean ovulatory women (n = 20); mean (+/- SD) body mass index 22.0 +/- 0.2 kg/m(2)). Lean women were categorized further according to whether they had polycystic-appearing ovaries (n = 8) or normal-appearing ovaries (n = 12). INTERVENTION(s): Controlled ovarian hyperstimulation and IVF. MAIN OUTCOME MEASURE(s): Serum estradiol, testosterone, and leptin. RESULT(s): Mean (+/- SD) leptin levels were significantly higher before and after GnRH agonist down-regulation in obese women (41.7 +/- 5.2 pg/mL and 36.1 +/- 5.8 pg/mL, respectively) compared with lean women (8.4 +/- 1.0 pg/mL and 6.9 +/- 1.1 pg/mL, respectively). Mean (+/- SD) leptin levels increased significantly in both groups (54.5 +/- 5.1 pg/mL and 11.7 +/- 1.2 pg/mL, respectively), and the mean (+/-SD) percentage increase was similar (55% +/- 18% and 54.8% +/- 17%, respectively). Mean (+/-SD) leptin levels were similar in women with polycystic-appearing and normal-appearing ovaries before controlled ovarian hyperstimulation, but increased significantly in women with polycystic-appearing ovaries afterward (14.7 +/- 1.8 pg/mL and 9.3 +/- 1.0 pg/mL, respectively). CONCLUSION(s): Significant increases in leptin levels occur during controlled ovarian hyperstimulation, suggesting that leptin plays a role in follicular growth and maturation. The exaggerated response in women with polycystic-appearing ovaries reflects either a greater number of recruited follicles or a predisposition of adipocytes to leptin production.     

Characterization of mild whole-body hyperthermia protocols using human breast, ovarian, and colon tumors grown in severe combined immunodeficient mice

OBJECTIVE: We have shown that one treatment of fever-like whole body hyperthermia (WBH) on mice bearing human breast tumors results in a tumor growth delay. Our goal was to repeat this study in mice bearing human ovarian or colon tumors. We further evaluated this WBH protocol by performing multiple and interrupted WBH treatments. METHODS: Human tumors were grown in severe combined immunodeficient (SCID) mice. For WBH, core body temperatures were maintained at 39.8+/-0.2 degrees C for 6-8 hours. Multiple treatments were given 6-7 days apart. Interrupted WBH consisted of three 2-hour heatings, 15 minutes apart. Tumor growth time (TGT) was the number of days to grow 1.5 or 2 times in volume. RESULTS: For WBH-treated ovarian tumors, TGT was 12+/-1.2d, compared with 5.0+/-0.1d for untreated mice (P < 0.05). For colon tumors with one WBH treatment TGT was 4.4+/-1.1d. Two and three treatments had TGTs of 9+/-2.3d and 8+/-1.6d. For the untreated tumors, TGT was 2+/-0.7d (P < 0.01 for one, two, and three treatments). Histological examination indicated that one and two treatments were associated with cellular damage within the tumors. With a slower growing colon tumor, the TGT was 24+/-3.3d with three WBH treatments, compared with 14+/-1.8d for controls (P < 0.01). The TGT of breast tumors treated with interrupted WBH was not significantly different than the noninterrupted, with TGT of 7.3+/-0.8d and 6.2+/-1.0d, respectively. CONCLUSIONS: These data illustrate that WBH causes a tumor growth delay in mice bearing human ovarian and colon tumors. This response is enhanced with a second treatment of WBH. Interrupted and noninterrupted WBH give comparable anti-tumor results. We will continue to evaluate WBH in various animal models to optimize its potential for clinical administration and maximize the anti-tumor response.     

Cell growth effects of leuprolide on cultured endometrioma cells

OBJECTIVE: To examine the effect of the GnRH agonist leuprolide on the growth of cultured endometrioma cells. STUDY DESIGN: Experimental study in an academic setting on endometrioma cell lines cultured from 15 women undergoing laparoscopy or laparotomy for excision of endometrioma. RESULTS: Mean cell counts resulting from treatment with lower concentrations were not significantly different from those of the controls. Increasing concentrations of leuprolide resulted in inhibition of cell growth. The inhibitory effect of leuprolide was statistically significant when the 1,000 ng/mL concentration was compared with the control concentration. CONCLUSION: Increased concentrations of leuprolide has suppressive effects on the growth of cultured endometrioma cells. This suggests a direct effect of GnRH agonists acting via GnRH agonist receptors. Long-acting gonadotropin-releasing hormone (GnRH) agonists cause pituitary receptor down-regulation and ovarian suppression, a function that has made this class of agents useful for the treatment of endometriosis. Recent work has also revealed that this class of agents may also have a direct suppressive effect on peripheral target tissue, mediated by GnRH and GnRH agonist receptors. Preliminary work has suggested that there are GnRH receptors in endometriotic cells and that the growth of these cells is inhibited by GnRH agonists. This activity, however, has not been extensively studied in the growth of endometrioma cells. The present study evaluated the effect of the GnRH agonist leuprolide on 15 endometrioma cell lines.     

Antitumor activity of irofulven against human ovarian cancer cell lines, human tumor colony-forming units, and xenografts

The objective of this study was to investigate the cytotoxic activity of irofulven (HMAF, MGI 114), a unique chemotherapeutic agent currently under clinical investigation, in various preclinical models of ovarian cancer. Antiproliferative effects of irofulven in ovarian cancer cell lines and ovarian tumor specimens were characterized in vitro using sulforhodamine B and human tumor colony-forming assays, respectively. Irofulven demonstrated marked activity against a panel of ovarian tumor cell lines, including IGROV1, OVCAR-3, OVCAR-4, OVCAR-5, OVCAR-8, and SK-OV-3, all of which exhibit various drug resistance mechanisms. In human tumor cloning assays, irofulven inhibited colony formation in surgically derived ovarian tumors at concentrations as low as 0.001 micro g /ml and indicated superior activity in comparison with paclitaxel when tested against the same tumor specimens. The antitumor activity of irofulven compared to that of paclitaxel was also examined using the SK-OV-3 xenograft model. In mice bearing subcutaneously implanted SK-OV-3 tumors, treatment with paclitaxel failed to inhibit tumor growth; whereas mice treated with maximum tolerated doses of irofulven had a 25% partial shrinkage rate, and the remaining animals had a mean tumor growth inhibition of 82%. The potent activity of irofulven against ovarian tumors in vitro and in vivo supports the evaluation of its clinical activity in ovarian cancer.     

Epithelial ovarian tumors and CA125 in premenarchal girls

PURPOSE: This is a review of our 18-year experience with premenarchal girls with epithelial ovarian tumors. Special attention was focused on the predictive value of CA125 serum levels. METHODS: Analysis of premenarchal patients with resected or biopsied ovarian masses from 1988 to 2005 was performed. Patient age, clinical presentation, operative procedures, histologic type of tumor, treatment and outcome were obtained. RESULTS: Six premenarchal girls (aged from 6 to 14 years) were surgically treated for epithelial tumors, representing 13% of all ovarian tumors at this age. Histological findings revealed cystadenoma in four girls, one with a mucinous borderline tumor and one with undifferentiated carcinoma. Tumor volume was higher than 400 cm3 in four girls. Sensitivity, specificity and positive predictive value of CA125 level for ovarian malignant epithelial tumors were 0.50, 0.50, and 0.33, respectively. The premenarchal girl with undifferentiated carcinoma in Stage III died after six months in spite of chemotherapy. CONCLUSION: Ovarian epithelial tumors in premenarchal girls show important growth potential and a relatively high malignancy rate with great influence of borderline neoplasms. CA125 is a tumor marker with low sensitivity and specificity for detection of epithelial ovarian malignancy in this age group.     

Protection of ovarian function and fertility using a combination of gonadotropin-releasing hormone (GnRH) agonist and GnRH antagonist during cancer treatment in young females.

Cytotoxic treatment can cause early loss of ovarian function associated with loss of fertility in younger women. To investigate if co-treatment with a combination of gonadotropin-releasing hormone (GnRH) agonist and GnRH antagonist may be useful in preserving ovarian function and fertility in younger women during chemotherapy, we prospectively observed nine young patients receiving different chemotherapies for various malignant diseases and other severe medical conditions who also received simultaneous GnRH agonist and GnRH antagonist. Mean age of the patients was 26.56 +/- 8.78 years, all were < or =35 years old. Eight (88.9%) patients regained normal basal hormonal profile within 3 - 6 months after the completion of chemotherapy. Median level of follicle-stimulating hormone, luteinizing hormone and estradiol was 6.3 +/- 8.8 U/l, 8.2 +/- 25.4 U/l and 118.0 +/- 130.8 pg/ml, respectively. Eight (88.9%) patients resumed spontaneous menses within 3 - 11 months following discontinuation of chemotherapy. Two (22.2%) patients conceived: one spontaneously, and the second following induction of ovulation by injection of gonadotropins. It seems that combined usage of GnRH agonist and GnRH antagonist during chemotherapy may be useful in preserving ovarian function and fertility in a group of young females receiving chemotherapy treatment.     

Gonadotropin-releasing hormone agonist treatment before abdominal myomectomy: a controlled trial

OBJECTIVE: To ascertain whether adjuvant gonadotropin-releasing hormone (GnRH) agonist therapy decreases blood loss during abdominal myomectomy. DESIGN: Randomized controlled trial. SETTING: Academic reproductive surgery center. PATIENT(S): One hundred premenopausal women requiring first-line conservative surgery for symptomatic intramural or subserous fibroids. INTERVENTION(S): Eight weeks of treatment with depot triptorelin before myomectomy or immediate surgery. MAIN OUTCOME MEASURES: Intraoperative blood loss, operating time, degree of difficulty of the procedure, and short-term rate of fibroid recurrence. RESULT(S): Mean (+/-SD) intraoperative blood loss was 265 +/- 181 mL in triptorelin recipients and 296 +/- 204 in patients who had immediate surgery (mean difference, -31 mL [95% CI, -108 to 46 mL]). No significant differences were observed in blood loss according to uterine volume, number of fibroids removed, or total length of myometrial incisions. Most procedures in either group were of routine difficulty. On ultrasonography 6 months after myomectomy, four women in the GnRH agonist group and one in the immediate surgery group had tumor recurrence. CONCLUSION(S): Treatment with a GnRH agonist before abdominal myomectomy has no significant effect on intraoperative blood loss. Thus, systematic use of medical therapy before abdominal myomectomy does not seem to be justified.