Spheroid Formation and Peritoneal Metastasis in Ovarian Cancer: The Role of Stromal and Immune Components.

Ovarian cancer (OC) is one of the most common gynecological cancers, with the worst prognosis and the highest mortality rate. Peritoneal dissemination (or carcinomatosis) accompanied by ascites formation is the most unfavorable factor in the progression and recurrence of OC. Tumor cells in ascites are present as either separate cells or, more often, as cell aggregates, i.e., spheroids which promote implantation on the surface of nearby organs and, at later stages, metastases to distant organs. Malignant ascites comprises a unique tumor microenvironment; this fact may be of relevance in the search for new prognostic and predictive factors that would make it possible to personalize the treatment of patients with OC. However, the precise mechanisms of spheroid formation and carcinomatosis are still under investigation. Here, we summarize data on ascites composition as well as the activity of fibroblasts and macrophages, the key stromal and immune components, in OC ascites. We describe current knowledge about the role of fibroblasts and macrophages in tumor spheroid formation, and discuss the specific functions of fibroblasts, macrophages and T cells in tumor peritoneal dissemination and implantation.

Plasma Exosomes of Patients with Breast and Ovarian Tumors Contain an Inactive 20S Proteasome.

Exosomes are directly involved in governing of physiological and pathological conditions of an organism through the transfer of information from producing to receiving cells. It can be assumed that exosomes are one of the key players of tumor dissemination since they are very stable and small enough to penetrate from various tissues into biological fluids and then back, thus interacting with tissue target cells. We evaluated the enzymatic activity and the level of 20S proteasome in tissue and exosomes of healthy females (n = 39) and patients with ovarian (n = 50) and breast (n = 108) tumors to reveal the critical role of exosomal cargo in the mediation of different types of metastases. Exosomes from plasma and ascites were isolated and characterized in according to International Society for Extracellular Vesicles guidelines. The level of 20S proteasome in tissue and exosomes was determined using Western blot analysis. Chymotrypsin- and caspase-like (ChTL and CL, respectively) peptidase activities of the proteasomes were determined using fluorogenic Suc-LLVY-AMC and Cbz-LLG-AMC substrates, respectively. We observed increased levels of 20S proteasome in ovarian cancer tissue and luminal B subtype breast cancer tissue as well as in plasma exosomes from cancer patients. Moreover, the level of the 20S proteasome in plasma exosomes and ascites exosomes in patients with ovarian tumors is comparable and higher in ovarian cancer patients with low volume ascites than in patients with moderate and high-volume ascites. We also found increased ChTL and CL activities in breast cancer and ovarian cancer tissues, as well as in peritoneal metastases in ovarian cancer, while proteasomal activity in exosomes from plasma of healthy females and all patients, as well as from ascites of ovarian tumor patients were lower than detection limit of assay. Thus, regardless of the type of tumor metastasis (lymphogenous or peritoneal), the exosomes of cancer patients were characterized by an increased level of 20S proteasome, which do not exhibit enzymatic activity.

Insulin-Like Growth Factors and Their Binding Proteins in Tumors and Ascites of Ovarian Cancer Patients: Association With Response To Neoadjuvant Chemotherapy

Purpose: Tumor cell growth and sensitivity to chemotherapy depend on many factors, among which insulin-like growth factors (IGFs) may play important roles. The aim of the present study was to evaluate the levels of insulin-like growth factors (IGFs) and IGF binding proteins (IGFBPs) in primary tumors and ascites as predictors of response to neoadjuvant chemotherapy in ovarian cancer (OC) patients. Materials and Methods: Tumor tissue samples and ascitic fluid were obtained from 59 patients with advanced OC. The levels of IGF-I, IGF-II, IGFBP-3, IGFBP-4 and PAPP-A were determined using ELISA kits. Taking into account the data on expression of these IGF-related proteins and outcome, logistic regression was performed to identify predictors of response to neoajuvant chemotherapy. Results: Human ovarian tumors expressed IGFs, IGFBP-3, IGFBP-4 and PAPP-A and these proteins were also present in ascites fluid and associated with its volume. IGFs and IGFBPs in ascites and soluble PAPP-A might play a key role in ovarian cancer progression . However, levels of proteins of the IGF system in tumors were not significant predictors of objective clinical response (oCR). Univariate analysis showed that the level of IGF-I in ascites was the only independent predictor for oCR. Conclusion: The level of IGF-I in ascites was shown to be an independent predictor of objective clinical response to chemotherapy for OC patients treated with neoadjuvant chemotherapy and debulking surgery.

Extraskeletal myxoid chondrosarcoma of the vulva: A case report.

Extraskeletal myxoid chondrosarcoma (ESMC) of the vulva is an extremely rare tumor and currently, there is little available information on its biological behavior and treatment strategy. The present study reports a case of recurrent ESMC of the vulva in a 32-year-old female. The patient presented with an increasingly painful mass of the right vulva, at the site of an exision which had been performed 7-months previously. The tumor mass was histopathologically diagnosed as primary ESMC of the vulva and subsequently, vulvectomy was performed. Cytological examination showed negative surgical margins. Intraoperative radiation therapy at a single dose of 10 Gy was administered to the bed of the removed tumor. The patient refused chemotherapy and five months after surgery, a new lesion was identified in the inguinal region. Bilateral inguinal-femoral lymph node dissection was performed and external beam radiation therapy at a dose of 40 Gy was administered to the inguinal region. Follow-up examination seven months after surgery revealed no evidence of disease progression and at present, the patient remains alive. This study highlights the importance of analyzing each clinical case of ESMC as this may lead to the development of guidelines for the optimal treatment of this rare tumor.