Chemosensitivity of BRCA1-Mutated Ovarian Cancer Cells and Established Cytotoxic Agents.

OBJECTIVE: Serous adenocarcinomas that arise in patients with inherited mutations in the tumor suppressor genes BRCA1 and BRCA2 are initially well treatable with platinum/paclitaxel. For recurrent disease in patients with BRCA1 or BRCA2 mutations, olaparib treatment is available. To study additional therapeutic regimens, a better understanding of the cellular and molecular mechanisms of the tumors in in vitro models is important. METHODS/MATERIALS: From a high-grade serous ovarian tumor of a BRCA1 mutation carrier, we established 3 distinct cell line subclones, OVCA-TR3.1, -2, and -3. Immunohistochemical characterization, flow cytometric analyses, chemosensitivity, and somatic mutation profiling were performed. RESULTS: The cell lines expressed AE1/AE3, Pax8, WT-1, OC125, estrogen receptor (ER), and p53, comparable to the primary tumor. Synergism could be shown in the combination treatment eremophila-1-(10)-11(13)-dien-12,8ß-olide (EPD), with cisplatin, whereas combination with olaparib did not show synergism. Eremophila-1-(10)-11(13)-dien-12,8ß-olide, a sesquiterpene lactone, is a novel chemotherapeutic agent. The inherited BRCA1 c.2989_2990dupAA mutation was confirmed in the cell lines. Loss of heterozygosity of BRCA1 was detected in each cell line, as well as a homozygous TP53 c.722C>A mutation. Flow cytometry showed that all cell lines had a distinct DNA index. CONCLUSIONS: Three new isogenic ovarian cancer cell lines were developed from a patient with a germ line BRCA1 mutation. Chemosensitivity profiling of the cell lines showed high tolerance for olaparib. Treatment with EPD proved synergistic with cisplatin. The effects of EPD will be further investigated for future clinical efficacy.

[Uterine fibroids complicated by haematometra]. / Hematometra als complicatie bij uterus myomatosus.

BACKGROUND: Uterine fibroids are common, benign tumours of the myometrium. The clinical symptoms include menorrhagia, abdominal pain and subfertility. CASE DESCRIPTION: A 37-year-old black woman known to have uterine fibroids presented at the gynaecology outpatient clinic with abdominal pain. Ultrasonography and an MRI scan revealed haematometra caused by an obstructive myoma, which was drained during a hysteroscopy. The patient was subsequently treated with gonadotrophin-releasing hormone (GnRH) agonist in order to reduce the myoma. Resection of the myoma will take place sometime in the future. CONCLUSION: Haematometra is an accumulation of blood in the uterine cavity. It is a rare complication of uterine fibroids and causes abdominal pain and enlargement of the uterus. Amenorrhoea is often a finding because an adequate outflow of menstrual blood is no longer possible. The primary treatment is to drain the haematometra; a subsequent myomectomy should be performed.

MRI for clinically suspected appendicitis during pregnancy.

OBJECTIVE: The purpose of this study was to evaluate whether MRI can be used to accurately diagnose or exclude appendicitis in pregnant patients with clinically suspected appendicitis. CONCLUSION: Our results suggest that MRI is helpful in the examination and diagnosis of acute appendicitis in pregnant patients. MRI may therefore be a good alternative to CT in pregnant patients for whom sonographic findings are nondiagnostic.