leuprolide and Endometrial-Neoplasms

Topics: 17 alpha-Hydroxyprogesterone Caproate; Antineoplastic Agents, Hormonal; Endometrial Neoplasms; Estrogens; Female; Gonadotropin-Releasing Hormone; Humans; Hydroxyprogesterones; Leuprolide; Medroxyprogesterone Acetate; Raloxifene Hydrochloride; Receptors, Progesterone; Selective Estrogen Receptor Modulators; Tamoxifen; Treatment Outcome

Topics: Anastrozole; Antineoplastic Agents, Hormonal; Aromatase Inhibitors; Chemotherapy, Adjuvant; Drug Therapy, Combination; Endometrial Neoplasms; Estrogens; Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Medroxyprogesterone Acetate; Nitriles; Postoperative Care; Tamoxifen; Treatment Outcome; Triazoles

This article is an overview of uterine neoplasms that demonstrate mesenchymal differentiation. Major clinical and pathologic features are described, with a focus on those lesions that cause diagnostic difficulty. Brief discussions on more recent observations made concerning these entities are also included.

Topics: Adenofibroma; Adenomyoma; Antineoplastic Agents, Hormonal; Endometrial Neoplasms; Female; Humans; Leiomyomatosis; Leuprolide; Myometrium; Receptors, Cell Surface; Sarcoma; Stromal Cells; Uterine Neoplasms; Uterus

Mitogenesis and mutagenesis are major driving forces in neoplastic development. Little is known about important breast mutagens, but much is known about breast mitogens. "Blocking" the effect of breast cell mitogens, by reducing the actual exposure of the breast to them, is an obvious strategy for breast cancer prevention. The ovarian hormones, estrogens and progesterone, are major effective (direct or indirect) breast cell mitogens. There is overwhelming epidemiologic evidence that breast cancer risk is closely related to exposure to estrogens and progestogens. A woman's exposure to endogenous ovarian estrogens and progesterone is drastically reduced by the use of combination-type oral contraceptives (COCs), but the exogenous synthetic estrogen and progestogen in the COC effectively replace the ovarian estrogen and progesterone, so that no decrease in breast cell exposure to these hormones is obtained. Doses of estrogen and progestogen in modern COCs are close to the minimum attainable, while still retaining both contraceptive efficacy and ovarian suppression (so that endogenous estrogen and progesterone do not add to the dose of estrogen and progestogen from the COC). Considerably lower effective breast cell exposure to estrogen and progestogen can, however, be achieved by using a gonadotropin-releasing hormone agonist to suppress ovarian function and compensating for the resulting hypoestrogenemia with low-dose hormone replacement. Such a contraceptive is predicted to reduce lifetime breast cancer risk by more than 50% if used for 10 years and by as much as 70% following 15 years of use. Contraception represents a unique opportunity to have a substantial beneficial impact on women's health; more than 10 million women use COCs daily in the United States.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Age Factors; Bone Density; Breast Neoplasms; Cardiovascular Diseases; Case-Control Studies; Cell Division; Contraceptives, Oral, Combined; Contraceptives, Oral, Hormonal; Drug Utilization; Endometrial Neoplasms; Endometrium; Estrogen Replacement Therapy; Estrogens; Female; Gonadotropin-Releasing Hormone; Humans; Hyperplasia; Incidence; Leuprolide; Middle Aged; Neoplasms, Hormone-Dependent; Osteoporosis; Ovarian Neoplasms; Pilot Projects; Premenopause; Progesterone; Progestins; Reproductive History; Risk Factors; Testosterone

Gonadotrophin-releasing hormone agonists (GnRHAs) were investigated as contraceptive agents from the late 1970's to the mid-1980's. They were abandoned as they appeared to offer no advantage over conventional combination-type oral contraceptives (COCs). This conclusion appears to be incorrect. We propose here a contraceptive regimen of a depot formulation of a GnRHA plus add-back estrogen and intermittent progestogen. The dose of add-back sex-steroids is substantially less than that in COCs; this reduction in sex-steroids should lead to a major reduction in lifetime breast cancer occurrence.

Topics: Bone and Bones; Breast Neoplasms; Contraceptive Agents, Female; Endometrial Neoplasms; Estrogens, Conjugated (USP); Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Lipid Metabolism; Liver; Medroxyprogesterone; Medroxyprogesterone Acetate; Ovarian Neoplasms; Ovary; Risk Factors

To evaluate the effectiveness and safety of leuprolide acetate in the treatment of endometriosis.. From Nov. 2007 to Oct. 2012, the patients who confirmed to be endometriosis were randomly divided into test group of 113 cases and control group of 116 cases. The test drug was the sustained-release agent of leuprolide acetate. The control drug was Enantone. The drugs were used for 3 times in total. After treatment, the ovarian mass volumes measured with type-B ultrasound, the scores of the patient's subjective symptoms during non-menstrual and menstruation days, the pelvic signs during non-menstrual days, the changes of hormones [estradiol (E2), FSH, LH], and adverse events were observed.. After the treatment, the rate of changes of ovarian mass volume (among them, at 12 weeks after the first injection, the median was -55.83% in the test group, -68.22% in the control group, P = 0.336), the distinct improvement rate of symptom scores and pelvic signs during non-menstrual days [among them, at 12 weeks after the first injection, the rate of lower abdomen pain was 47.5% (48/101) in the test group, 44.0% (44/100) in the control group, P = 0.881], the hormone (E2, FSH, LH) levels [among them, at 12 weeks after the first injection, the serum level of E2, was (33±38) pmol/L in the test group, (38±40) pmol/L in the control group, P = 0.414; the serum level of FSH, was (5.1±2.8) U/L in the test group, (5.3±2.3) U/L in the control group, P = 0.666; the serum level of LH, was (0.6±0.8) U/L in the test group, (0.6±0.9) U/L in the control group, P = 0.907], had no statistically significant difference between the two groups (all P > 0.05). The distinct improvement rate and improvement rate of symptom (lower abdomen pain, low back pain) scores during menstruation days at 12 weeks after the first injection, the rates of lower abdomen pain were 73.9% (34/46), 15.2% (7/46) respectively in the test group, 72.3% (34/47), 2.1% (1/47) respectively in the control group, had statistically significant difference between the two groups (P = 0.026). There was no serious adverse event occurred in both two groups. The incidence rate of adverse event was 33.6% (38/113) in test group, 23.2% (27/116) in control group, there was no significant difference between the two groups (P = 0.082).. Leuprolide acetate is effective and safe in the treatment of endometriosis.

Topics: Antineoplastic Agents, Hormonal; Delayed-Action Preparations; Double-Blind Method; Endometrial Neoplasms; Endometriosis; Estradiol; Female; Hormones; Humans; Leuprolide; Treatment Outcome

In this article, we present the results of organ-preserving treatment applied in 24 patients of reproductive age with atypical endometrial hyperplasia or early-stage endometrial cancer. All of them would like to preserve their reproductive potential. Thirteen women with atypical endometrial hyperplasia were treated with the combination of six intramuscular injections of 3.75 mg gonadotropin-releasing hormone agonist (GnRHa)--leuproreline acetate depot every 4 weeks. After the third injection of 3.75 mg of leuproreline acetate, the levonorgestrel intrauterine hormonal system containing 52 mg levonorgestrel (Mirena®, Bayer, Germany) was inserted for at least 6 months. In 11 women with stage IA well-differentiated endometrial adenocarcinoma, hormonal therapy included nine intramuscular injections of 3.75 mg of GnRHa every 4 weeks. After the third injection of 3.75 mg of GnRHa, we also inserted a GnRH-IUS (Mirena®) for at least 12 months. This type of therapy was effective for all these patients and may be offered to be used as an alternative to surgery in women with atypical endometrial hyperplasia or early stage 1A well-differentiated endometrial cancer in women of reproductive age. Three women with endometrial cancer became pregnant and two of them delivered at term and one has an ongoing pregnancy.

Topics: Adenocarcinoma; Administration, Intravaginal; Adult; Antineoplastic Agents, Hormonal; Delayed-Action Preparations; Drug Delivery Systems; Drug Therapy, Combination; Endometrial Hyperplasia; Endometrial Neoplasms; Female; Gonadotropin-Releasing Hormone; Humans; Injections, Intramuscular; Leuprolide; Levonorgestrel; Neoplasm Staging; Organ Sparing Treatments; Pilot Projects; Progestins; Young Adult

In order to determine the efficacy and toxicity of the gonadotrophin-releasing hormone agonist Leuprolide in the management of patients with recurrent or metastatic endometrial cancer, we performed a phase II study. Patients were included if there was clinical or radiological documentation of bidimensionally measurable recurrent or metastatic endometrial cancer that was deemed incurable. Treatment was 7.5 mg i.m. every 28 days, and was to continue for at least 2 courses until evidence of disease progression, patient requested withdrawal, or unacceptable toxicity. Twenty-five patients received Leuprolide for recurrent or metastatic endometrial cancer. The median age at study entry was 62 years, and the median time from initial diagnosis to first course of Leuprolide was 25 months. Six patients had received no systemic or radiotherapy prior to study entry, and 2 of these had not previously undergone hysterectomy. Fifteen patients received prior pelvic radiotherapy and 3 patients received prior whole abdominal radiotherapy. Nine of the 25 patients had received prior progestational agents, and 2 had received prior systemic chemotherapy. There were no responders, 8 patients had stable disease for a median 5 months (range 1-8), 14 patients progressed on therapy, and 3 patients were not evaluable for response due to receiving only 1 treatment. One patient experienced a grade 3 toxicity that was possibly attributable to Leuprolide (deep venous thrombosis). The median survival from study entry was 6 months. Twelve patients received progesterone after discontinuing this study, and none responded. Leuprolide does not appear to be a clinically active agent in the treatment of recurrent or metastatic endometrial cancer.

Topics: Adult; Aged; Antineoplastic Agents, Hormonal; Endometrial Neoplasms; Female; Follow-Up Studies; Humans; Leuprolide; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplasm Staging

A progressive delay in the age of first conception results in an increased frequency of endometrial cancer patients in reproductive age and desiring childbearing.. A 38-year-old infertile woman with stage I endometrioid adenocarcinoma was treated with gonadotropin releasing hormone agonist (GnRHa) and levonorgestrel-releasing intrauterine device (LNG-IUD). After disease remission, she underwent a controlled ovarian stimulation for standard in vitro fertilization (IVF) program and had a pregnancy delivering a healthy male baby. Total laparoscopic hysterectomy with bilateral salpingo-oophorectomy was performed four months after delivery. The patient is free of disease after 3-year follow-up.. GnRHa plus LNG-IUD followed by IVF program is a safe and effective fertility-sparing strategy to manage infertile patients with stage I endometrial cancer.

Topics: Adult; Antineoplastic Agents, Hormonal; Carcinoma, Endometrioid; Contraceptive Agents, Female; Delayed-Action Preparations; Endometrial Neoplasms; Endometrium; Female; Fertility Preservation; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Intrauterine Devices, Medicated; Leuprolide; Levonorgestrel; Neoplasm Staging; Pregnancy; Remission Induction; Term Birth

We investigated the relationship between the antiproliferative effect of GnRH agonist and telomerase activity using the endometrial cancer cell line HEC-1A. The subjects were 38 endometrial cancer, and 2 atypical endometrial hyperplasia patients. GnRH-R expression was detected using RT-PCR. HEC-1A cells were incubated with 10(-7)-10(-4) M GnRH agonist (leuprolide acetate), and cell proliferation was determined using MTT assay. The telomerase activity was detected by the TRAP assay and expression of human telomerase reverse transcriptase (hTERT) was assessed by RT-PCR. GnRH-R mRNA was detected at 94.7% (36/38) in endometrial cancer and in both of the atypical endometrial hyperplasia and in HEC-1A cells. Cell proliferation of HEC-1A showed significant inhibition at leuprolide acetate concentrations of 10(-6) M or higher compared with untreated control culture (p<0.05). The telomerase activity showed no marked difference compared with untreated culture. However, hTERT mRNA expression showed a decrease in the leuprolide-treated cells. It is suggested that the mechanism of the antitumor effect of GnRH agonist involved the inhibition of hTERT mRNA expression in the endometrial cancer cells.

Topics: Cell Division; DNA-Binding Proteins; Endometrial Neoplasms; Female; Gene Expression; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Receptors, LHRH; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Neoplasm; Telomerase; Tumor Cells, Cultured

The antiproliferative effect of two GnRH agonists (leuprorelin acetate and triptorelin), alone or combined with tamoxifen (TAM) or medroxyprogesterone acetate (MPA), on human estrogen-sensitive endometrial cancer cells (Ishikawa) was investigated. Although ineffective when tested alone in all the culture conditions used, both analogues counteracted or even suppressed the estrogen-stimulated growth of Ishikawa cells. The antiestrogenic effect of TAM or MPA was not modified by their association with high doses of the GnRH analogues, but low concentrations of triptorelin combined with MPA 10(-7) M determined a reduction in cell numbers which was greater than that obtained with the progestin or the analogue alone. In addition, analogue treatment prevented the estrogen-induced decrease in the level of estrogen receptors. Our data provide evidence that GnRH agonists can directly inhibit estrogen-stimulated endometrial cancer cell growth and suggest that they may interfere with steroid-receptor machinery.

Topics: Antineoplastic Agents, Hormonal; Cell Division; Drug Synergism; Endometrial Neoplasms; Estrogen Receptor Modulators; Estrogens; Female; Gonadotropin-Releasing Hormone; Humans; Immunohistochemistry; Leuprolide; Medroxyprogesterone Acetate; Receptors, Estrogen; Receptors, Progesterone; Tamoxifen; Triptorelin Pamoate; Tumor Cells, Cultured

We report here a case of a patient affected by endometrial cancer and treated primarily with leuprolide, the surgical approach being unfeasible due to her compromised conditions. The therapy was continued for more than 6 years, and no progression of the disease was observed. During this period, some histological and immunohistochemical evaluations of the tumour (morphology, grading, proliferation and apoptotic index, E-cadherin expression) were performed. Furthermore, the expression of m-RNA for luteinizing-hormone releasing hormone (LHRH) receptors was determined. The results showed a discrepancy between some biological parameters of the tumour and its clinical characteristics. In fact, despite features suggestive of a progression of the cancer (such as the increase of both tumour grading and proliferating capacity (MIB-1), and a fall in the reparative process (appearance of mutated p53, reduced expression of both bcl-2 and c-erb-2) being detected, neither local invasion nor metastatic lesions were clinically observed. This discrepancy might be due to the maintenance of high levels of E-cadhezin. Moreover, since this tumour was shown to express mRNA for LHRH receptors, new evidence is provided about the favourable impact of LHRH analogue treatment in patients affected by endometrial cancer.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents, Hormonal; Biomarkers, Tumor; Disease Progression; Disease-Free Survival; Endometrial Neoplasms; Female; Humans; Leuprolide; Neoplasm Proteins; Receptors, LHRH; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

We studied the effects of luteinising hormone-releasing hormone (LHRH) agonist leuproreline (1 microM for 96 h) and LHRH antagonist cetrorelix on the cell growth of primary cultures from nine human endometrial cancers using the sulphorhodamine colorimetric test. Histological examinations and reverse transcription and polymerase chain reaction amplification (RT-PCR) for LHRH receptors were also performed. The endometrial cancers examined had a medium to high degree of proliferative activity and a low degree of apoptotic power; furthermore, they expressed the LHRH receptor RNA variably, detectable in 71% of cases. The addition of leuproreline or cetrorelix to cell cultures inhibited growth in a statistically significant way compared to untreated control cells; nevertheless, the percentage of cell growth inhibition obtained was very variable. These data suggest that LHRH analogues can exert differential inhibitory effects on the growth of endometrial cancer, which seems to be independent of the expression of specific LHRH receptors.

Topics: Aged; Cell Division; Endometrial Neoplasms; Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Middle Aged; Postmenopause; Receptors, LHRH; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tumor Cells, Cultured

We describe a low-grade endometrial stromal sarcoma coexistent with leiomyoma and adenomyosis treated with leuprolide acetate. We describe its histologic characteristics and clinical significance.

Topics: Adult; Endometrial Neoplasms; Endometriosis; Female; Humans; Leiomyoma; Leuprolide; Neoplasms, Multiple Primary; Sarcoma

Endometrial stromal nodule is a rare subtype of endometrial stromal tumor. Although such nodules are benign, hysterectomy has been considered the treatment of choice, because evaluation of the margin is required for diagnosis. The similarity between low-grade stromal sarcoma and stromal nodule suggests that stromal nodules might respond to hormonal management.. Twenty-one-year-old nulligravida, diagnosed with endometrial stromal nodule, which decreased in size with leuprolide acetate treatment, underwent local excision of the tumor with preservation of reproductive function.. Hormonal therapy was successful in decreasing the size of this stromal nodule which allowed for conservative management.

Topics: Adult; Antineoplastic Agents, Hormonal; Combined Modality Therapy; Drug Administration Schedule; Endometrial Neoplasms; Female; Humans; Injections, Intramuscular; Leuprolide; Sarcoma, Endometrial Stromal

Fas ligand induces cell death by means of apoptosis in a variety of cell types when cross-linked with its natural receptor, Fas. GnRH receptor-bearing tumors undergo apoptosis in vivo and in vitro with GnRH agonists. To provide a potential association of the Fas system with the antiproliferative signaling process of GnRH receptor, we have evaluated the regulation of Fas ligand expression in GnRH receptor-positive tumors and cloned cell lines known to have substantial GnRH receptors. Surgically removed uterine endometrial carcinomas and ovarian carcinomas had been screened for GnRH receptor expression before analysis. Fas ligand protein was characterized by immunoblotting of membrane proteins with the specific antibody. Fas ligand messenger RNA was determined by RT-PCR using oligonucleotide primers synthesized according to the published Fas ligand sequence. Incubation with a GnRH analog (1 mumol/L) induced the expression of Fas ligand messenger RNA and immuno-reactive Fas ligand with a lag time of 48 h in cloned cell lines (endometrial carcinoma HHUA cells, and ovarian carcinoma SK-OV-3 and Caov-3 cells). There was no detectable Fas ligand expression within 24 h. The stimulatory effect of GnRH on Fas ligand protein expression revealed a dose dependency; a half-maximal effect occurred with 10 nmol/L GnRH analog (P < 0.01). The stimulated Fas ligand expression could be neutralized by displacement of GnRH from its receptor by GnRH antagonist antide. Cells isolated from GnRH receptor-bearing ovarian carcinomas and uterine endometrial carcinomas gave identical results to those obtained in cloned cell lines. These data demonstrate the functional coupling of stimulated Fas ligand expression to GnRH receptor activation. Increased Fas ligand level within the GnRH receptor-bearing tumors might promote apoptotic cell death through attack on intratumoral Fas-positive cells that could, at least in part, account for the antiproliferative action of the hormone.

Topics: Apoptosis; Buserelin; Endometrial Neoplasms; fas Receptor; Female; Gene Expression; Humans; Leuprolide; Oligopeptides; Ovarian Neoplasms; Polymerase Chain Reaction; Receptors, LHRH; RNA-Directed DNA Polymerase; RNA, Messenger; Tumor Cells, Cultured

Gonadotropin-releasing hormone (GnRH) receptor-bearing tumors undergo apoptosis in vivo and in vitro with GnRH analogs. We recently showed that GnRH stimulation induces intratumoral expression of the apoptosis-inducing Fas ligand in human reproductive tract tumors. To provide a potential association of Fas/Fas ligand system with the antiproliferative signaling process of GnRH receptor, we evaluated a correlation between the Fas ligand expression and the number of viable cells in two types of GnRH receptor-bearing endometrial carcinomas that differ in Fas content. Surgically removed uterine endometrial carcinomas had been screened for the presence of GnRH receptor and Fas before analyses. Fas ligand protein was characterized by immunoblotting of membrane proteins with the specific antibody. After a lag time of 2 days, incubation with a GnRH analog leuprolide (10 microM) induced significant growth inhibition of the Fas- and GnRH receptor-bearing cells (p<0.01). Time course analysis showed that Fas ligand production, which was already observed at day 2 (p<0.01), precedes the onset of reduction in viable cell number. The stimulatory effect of GnRH on Fas ligand expression and reduction of viable cells revealed dose-dependency. The analog at concentration of 10 microM induced up to 90% reduction in cell number. In contrast, the growth of Fas-negative cells was not affected by the analog, although Fas ligand appeared in response to the GnRH analog (p<0.01). These data demonstrate that the co-presence of Fas could be essential for GnRH to promote antiproliferative action in endometrial cancer cells carrying GnRH receptor. The hormone may act through intratumor Fas and Fas ligand system to induced growth inhibition in GnRH-sensitive tumors.

Topics: Adenocarcinoma; Antineoplastic Agents, Hormonal; Cell Death; Endometrial Neoplasms; Fas Ligand Protein; fas Receptor; Female; Humans; Leuprolide; Membrane Glycoproteins; Receptors, LHRH; Tumor Cells, Cultured

In addition to its function as a key hormone in the regulation of the pituitary-gonadal axis, luteinizing hormone-releasing hormone (LHRH) probably also affects various extrapituitary tissues. LHRH binding sites and in vitro antiproliferative effects of LHRH analogues have been reported in human endometrial cancer. The effects of the LHRH agonist leuproreline and LHRH antagonist antide were studied on the cell growth, DNA synthesis, and cell cycle distribution of the human endometrial cancer cell lines HEC-1A and HEC-1B by the sulforhodamine B (SRB) method, [3H]thymidine assay incorporation, and propidium iodide DNA staining, respectively. In the presence of 1.0-100 microM leuproreline the proliferation of HEC-1A cells was significantly reduced as early as 3 days after drug exposure, with a minimum growth value of 69.9 +/- 3.6% (mean +/- SE) at the highest concentration tested (100 microM). Similar antiproliferative effects were obtained following a 6-day treatment with the LHRH antagonist antide. Also, inhibitory effects on [3H]thymidine incorporation into the DNA of the HEC-1A cell line were noted after a 6-day exposure to both LHRH analogues, in the above-mentioned concentration range. Cell cycle analysis of HEC-1A cells cultured in the presence of 10 microM leuproreline and antide showed a slight accumulation of cells in the G0/G1 phase, while the proportions of cells in the S and G2/M phases concomitantly decreased. No significant effects on proliferation, DNA synthesis, and cell cycle distribution were observed in HEC-1B cells with either leuproreline or antide (up to 100 and 10 microM, respectively) after a 6-day exposure. Both Northern blot analysis and reverse transcription polymerase chain reaction failed to detect expression of mRNA for the LHRH receptor in both HEC-1A and HEC-1B cell lines. In addition, the LHRH analogues did not affect the intracellular free calcium concentration, indicating that the classic signal transduction for LHRH is absent or impaired in HEC-1A cells. The observed direct inhibitory actions on HEC-1A cells support the concept that the two LHRH analogues may exert biological effects via cellular effectors distinct from the "classic" LHRH receptor. Although the mechanism by which these direct actions are produced is still obscure, these results might help to establish the basis for new approaches to the therapy of endometrial cancer.

Topics: Antineoplastic Agents, Hormonal; Cell Division; DNA; Endometrial Neoplasms; Female; Humans; Leuprolide; Receptors, LHRH; RNA; Tumor Cells, Cultured

A 46-year-old women presented with an inoperable low-grade endometrial stromal sarcoma. Two doses of Depo-Lupron, 7.5 mg, and Megace, 160 mg/day, were given to control uterine bleeding and shrink the tumor mass. In 9 weeks, significant reduction in the tumor occurred allowing for surgical resection. Total abdominal hysterectomy with bilateral salpingo-oophorectomy is the mainstay for primary treatment. The role of chemotherapy, radiation therapy, and hormonal therapy is poorly defined. This is a case report of neoadjuvant hormonal therapy which may improve outcomes in patients with endometrial stromal sarcomas. Additional research is needed to define the exact role of these agents.

Topics: Antineoplastic Agents, Hormonal; Endometrial Neoplasms; Female; Humans; Leuprolide; Megestrol Acetate; Middle Aged; Sarcoma, Endometrial Stromal

Topics: Aged; Antineoplastic Agents, Hormonal; Endometrial Neoplasms; Female; Humans; Leuprolide; Middle Aged; Neoplasm Staging; Publishing; Treatment Failure

We have previously documented the responsiveness of a cell line of human ovarian epithelial carcinoma (Bowman Gray 1) heterotransplanted in nude mice to treatment with the GnRH agonist Lupron-SR. In this study we used another human ovarian epithelial carcinoma cell line, OVCAR-3, and the human endometrial carcinoma cell line HEC-1A. After a latent period, OVCAR-3 tumors showed significant inhibition of growth on Days 17, 21, and 24 (P < 0.03) compared to controls. The effect was transient and did not persist beyond Day 24. HEC-1A tumors showed no inhibition of growth. Radioreceptor assay studies utilizing native radiolabeled GnRH and [D-Lys6]-GnRH revealed no specific GnRH receptors in any of the tumor samples (BG-1, OVCAR-3, HEC-1A, University of Nebraska cell line, and two fresh human ovarian epithelial tumor samples) compared to male rat anterior pituitary cells. Binding studies and the latency and transience of effect would suggest that the mechanism of action in this animal model may be indirect. This activity may be via altered circulating steroids, gonadotropins, cell-cycle regulatory events, or some other as-yet-undefined action related to GnRH agonist administration or indirectly via effects of the metabolic products of degraded GnRH agonist such as D-amino acids, which are incorporated into the cells by constitutive or adsorptive pinocytosis. This study confirms latency and transience of effect of GnRH agonist therapy on an in vivo model of ovarian cancer.

Topics: Animals; Carcinoma; Disease Models, Animal; Endometrial Neoplasms; Female; Humans; Leuprolide; Male; Mice; Mice, Nude; Neoplasm Transplantation; Ovarian Neoplasms; Pituitary Gland, Anterior; Radioligand Assay; Random Allocation; Receptors, LHRH; Tumor Cells, Cultured