Receptors for luteinizing hormone-releasing hormone (GnRH) as therapeutic targets in triple negative breast cancers (TNBC).

Triple negative breast cancers express receptors for gonadotropin-releasing hormone (GnRH) in more than 50% of the cases, which can be targeted with peptidic analogs of GnRH, such as triptorelin. The current study investigates cytotoxic activity of triptorelin as a monotherapy and in treatment combinations with chemotherapeutic agents and inhibitors of the PI3K and the ERK pathways in in vitro models of triple negative breast cancers (TNBC). GnRH receptor expression of TNBC cell lines MDA-MB-231 and HCC1806 was investigated. Cells were treated with triptorelin, chemotherapeutic agents (cisplatin, docetaxel, AEZS-112), PI3K/AKT inhibitors (perifosine, AEZS-129), an ERK inhibitor (AEZS-134), and dual PI3K/ERK inhibitor AEZS-136 applied as single agent therapies and in combinations. MDA-MB-231 and HCC1806 TNBC cells both expressed receptors for GnRH on messenger (m)RNA and protein level and were found sensitive to triptorelin with a respective median effective concentration (EC50) of 31.21 ± 0.21 and 58.50 ± 19.50. Synergistic effects occurred when triptorelin was combined with cisplatin. In HCC1806 cells, synergy occurred when triptorelin was applied with PI3K/AKT inhibitors perifosine and AEZS-129. In MDA-MB-231 cells, synergy was observed after co-treatment with triptorelin and ERK inhibitor AEZS-134 and dual PI3K/ERK inhibitor AEZS-136. GnRH receptors on TNBC cells can be used for targeted therapy of these cancers with GnRH agonist triptorelin. Treatment combinations based on triptorelin and PI3K and ERK inhibitors and chemotherapeutic agent cisplatin have synergistic effects in in vitro models of TNBC. If confirmed in vivo, clinical trials based on triptorelin and cisplatin could be quickly carried out, as triptorelin is FDA approved for other indications and known to be well tolerated.

A three-year review of treatment of cervical intraepithelial neoplasia with large loop excision of the transformation zone.

One hundred and eighty-five patients were treated with large loop excision of the transformation zone for cervical intraepithelial neoplasia from October 1992 through September 1994. All patients were followed up regularly until September 1995 to review the outcome and morbidity. Cure rates of 97.2% in the first six months and 95.4% at the end of the first 12 months were obtained. Thirteen patients (7.0%) were admitted as emergency cases for post-operative haemorrhage, which required suturing, cauterisation with silver nitrate or electrocoagulation, vaginal douching, or antibiotic treatment. One patient developed cervical stenosis and incomplete excisions were noted in 46 (24.9%) patients. Eleven (6.0%) patients had cervical carcinomas detected. Our findings further confirm that this method is a reliable and safe way to treat cervical intraepithelial neoplasia with an acceptable rate of morbidity.