Ovarian cancer is the second most common gynaecologic malignancy and the main cause of death from gynaecologic cancer, due to late diagnosis and chemoresistance. Studies have reported the role of cysteine in cancer, by contributing for hydrogen sulphide (H2S) generation and as a precursor of glutathione (GSH). However, the role of cysteine in the adaptation to hypoxia and therapy response remains unclear. We used several ovarian cancer cell lines, ES2, OVCAR3, OVCAR8, A2780 and A2780cisR, to clarify cysteine relevance in ovarian cancer cells survival upon hypoxia and carboplatin. Results show that ES2 and OVCAR8 cells presented a stronger dependence on cysteine availability upon hypoxia and carboplatin exposure than OVCAR3 cells. Interestingly, the A2780 cisR, but not A2780 parental cells, benefits from cysteine upon carboplatin exposure, showing that cysteine is crucial for chemoresistance. Moreover, GSH degradation and subsequent cysteine recycling pathway is associated with ovarian cancer as seen in peripheral blood serum from patients. Higher levels of total free cysteine (Cys) and homocysteine (HCys) were found in ovarian cancer patients in comparison with benign tumours and lower levels of GSH were found in ovarian neoplasms patients in comparison with healthy individuals. Importantly, the total and S-Homocysteinylated levels distinguished blood donors from patients with neoplasms as well as patients with benign from patients with malignant tumours. The levels of S-cysteinylated proteins distinguish blood donors from patients with neoplasms and the free levels of Cys in serum distinguish blood from patients with benign tumours from patients with malignant tumours. Herein we disclosed that cysteine contributes for a worse disease prognosis, allowing faster adaptation to hypoxia and protecting cells from carboplatin. The measurement of serum cysteine levels can be an effective tool for early diagnosis, for outcome prediction and follow up of disease progression.

Benign metastasizing leiomyomatosis (BML) is a rare disease that typically occurs in women with a history of uterine leiomyomatosis. Benign metastasizing leiomyomatosis occurs more frequently in the lungs but may also develop in other organs and tissues. Other unusual variants of extra-uterine leiomyomatosis include intravenous leiomyomatosis (IVL) and leiomyomatosis peritonealis disseminata (LPD). In this article, three cases of BML are presented. One case, in a premenopausal woman, presented cutaneous metastases. We also present a case of IVL and a case of LPD, which occurred in postmenopausal women. Given the rarity of BML, IVL, and LPD, the authors reviewed the literature and herein discuss the implications for treatment in all five cases. Evidence for treating BML, IVL, and LPD is still scarce, and data available from our series and other small series seem to point to the patient’s hormonal status playing a fundamental part in the treatment plan. Furthermore, a collecting bag when performing excision of uterine leiomyomas may help avoid the potential spreading of leiomyomatosis. Hysterectomized patients with chronic cough, frequent respiratory infections, abdominal discomfort, right heart failure, or non-specific symptoms should be actively screened for BML, IVL, and LPD. Treatment should be individualized according to each patient’s hormonal status and desires.

Summary Thirty-one consecutive patients with relapsed or refractory GCT received an HDT schedule including carboplatin, the dose of which was adjusted to measured glomerular filtration rate. There was one HDT-associated death (3%), due to acute renal failure. The 3-year probability of overall and disease-free survival for 21 patients with primary refractory disease or responsive relapse was 60% and 42%, respectively, while none of ten patients with refractory relapse have survived disease free.

Background Epithelial ovarian cancer (EOC) is an aggressive and lethal malignancy and novel EOC cell lines with detailed characterization are needed, to provide researchers with diverse helpful resources to study EOC biological processes and cancer experimental therapies. Methods The IPO43 cell line was established from the ascitic fluid of a patient with a diagnosis of high-grade serous carcinoma (HGSC) of the ovary, previously treated with chemotherapy. Cell immortalization was achieved in 2D cell culture and growth obtained in 2D and 3D cell cultures. The characterization of immortalized cells was done by immunocytochemistry, flow cytometry, cell proliferation, chromosomal Comparative Genomic Hybridization (cCGH), STR profile and Next Generation Sequencing (NGS). Results Characterization studies confirmed that IPO43 cell line is of EOC origin and maintains morphological and molecular features of the primary tumor. cCGH analysis showed a complex profile with gains and losses of specific DNA regions in both primary ascitic fluid and cell line IPO43. The cell line was successfully grown in a 3D system which allows its future application in more complex assays than those performed in 2D models. IPO43 cell line is resistant to standard drug treatment in vitro. Conclusions IPO43 is available for public research and we hope it can contribute to enrich the in vitro models addressing EOC heterogeneity, being useful to investigate EOC and to develop new therapeutic modalities.

Objective: to review the most recent data on the impact of the primary treatment and individual factors on ovarian cancer patient survival and to study it in a real world population. Methods/materials: retrospective analysis of 147 consecutive ovarian cancer patients treated with platin-based chemotherapy, either after primary debulking surgery (PDS) (n = 94, 64%) or as neoadjuvant (NACT) treatment (53, 36%). Results: NACT patients were older (64.3 vs. 58.2 years), with radiologically unresectable disease (74%) and/or comorbidities (26%). Fifty-five percent of pts. submitted to PDS were staged III/ IV. Serous carcinomas were equally distributed (PDS-57% vs. NACT-60%) but endometrioid (20 vs. 4%) and carcinomas not otherwise specified (6 vs. 30%) were more frequently diagnosed in the PDS and NACT group, respectively. Genetic diagnosis (24.4%): 11 BRCA1/2 and 1 RAD51C carriers identified. Residual disease after surgery was the only significant prognostic factor for both relapse (HR = 2267) and death (HR = 1847). Primary debulking surgery was associated with a significantly better PFS (HR = 0.541; p = 0.012) and with a trend to a better OS (HR = 0.714; p = 0.296). For pts. with III/IV disease OS was significantly superior in the PDS group. Conclusion: residual disease was the only significant prognostic factor. Primary surgery was associated with a significantly better PFS. The difference in OS was significant in stage III/IV patients. This reinforces the importance of maximal cytoreduction.