Neuropilin 1 in uterine leiomyosarcoma. Clinical and pathological analysis

Objectives: The role of angiogenesis in leiomyosarcomas still remains unclear. The aim of this study was to evaluate the NRP1 expression in the leiomyosarcoma tissues and to find the relations between its expression and the clinical features. Material and methods: The study group consisted of 50 patients with diagnosis of the uterine leiomyosarcoma. Clinical and follow up data were collected. Using immunohistochemical methods the expression of NRP1 was detected. Results: The lack of NRP1 expression was found in 14 cases, positive (weak or moderate) expression was noted in 36 cases. The significantly higher expression of NRP1 was observed in more severe clinical stages in comparison to lower stages of the disease. The significantly shorter survival of patients with the positive expression of NRP1 in leiomyosarcoma was observed. Conclusions: The expression of NRP1 is associated with clinical advancement and worse prognosis in uterine LMS. Neuropilin 1 can be widely used as a postoperative survival predictor for the patients suffering from uterine LMS

Clinical Relevance and Immunosuppressive Pattern of Circulating and Infiltrating Subsets of Myeloid-Derived Suppressor Cells (MDSCs) in Epithelial Ovarian Cancer

Myeloid-derived suppressor cells (MDSCs) expansion is a hallmark of cancer. Three major MDSC subsets defined as monocytic (M)-MDSCs, polymorphonuclear (PMN)-MDSCs and early stage (e)MDSCs can be revealed in human diseases. However, the clinical relevance and immunosupressive pattern of these cells in epithelial ovarian cancer (EOC) are unknown. Therefore, we performed a comprehensive analysis of each MDSC subset and immunosupressive factors in the peripheral blood (PB), peritoneal fluid (PF), and the tumor tissue (TT) samples from EOC and integrated this data with the patients' clinicopathological characteristic. MDSCs were analyzed using multicolor flow cytometry. Immunosuppressive factors analysis was performed with ELISA and qRT-PCR. The level of M-MDSCs in the PB/PF/TT of EOC was significantly higher than in healthy donors (HD); frequency of PMN-MDSCs was significantly greater in the TT than in the PB/PF and HD; while the level of eMDSCs was greater in the PB compared with the PF and HD. Elevated abundance of tumor-infiltrating M-MDSCs was associated with advanced stage and high grade of EOC. An analysis of immunosuppressive pattern showed significantly increased blood-circulating ARG/IDO/IL-10-expressing M- and PMN-MDSCs in the EOC patients compared with HD and differences in the accumulation of these subsets in the three tumor immune microenvironments (TIME). This accumulation was positively correlated with levels of TGF-β and ARG1 in the plasma and PF. Low level of blood-circulating and tumor-infiltrating M-MDSCs, but neither PMN-MDSCs nor eMDSCs was strongly associated with prolonged survival in ovarian cancer patients. Our results highlight M-MDSCs as the subset with potential the highest clinical significance

Does the patients age at cancer diagnosis affect microvessels density in uterine sarcoma tissues?

Objectives: The objective of the study was to retrospectively evaluate the density of vessels exhibiting positive glycoprotein CD34 expression in the uterine leiomyosarcoma tissues and their correlation with the age of patients at the time of tumor diagnosis. Material and methods: The archival paraffin blocks with the cancer tissues collected from 50 patients suffering from uterine leiomyosarcoma were used together with their clinical and demographic data. The immunohistochemical peroxidase-de­pendent methods were used to detect microvessels with positive CD34 expression. The glycoprotein CD34 expression was evaluated as a density of microvessel showing the positive immunohistochemical reaction (MVDCD34). Results: The negative, statistically significant correlation between the age of patients (at the moment diagnosis) and the MVDCD34+ (R = –0.289, p = 0.042) was found. Conclusions: The study’s findings may suggest that the tissues of younger people constitute a permissive environment for pro-angiogenic factors

Isobolographic analysis demonstrates the additive and synergistic effects of gemcitabine combined with fucoidan in uterine sarcomas and carcinosarcoma cells

Background: Uterine sarcomas and carcinosarcoma are associated with unfavorable prognosis. The regimens that are used in chemotherapy are associated with high incidence of side effects and usually do not significantly increase patients’ survival rates. In this study we investigated the activity and interactions between gemcitabine and fucoidan, the natural compound known for its anti-tumor properties, in human sarcomas and carcinosarcoma cell models. Methods: SK-UT-1, SK-UT1-B (carcinosarcoma), MES-SA (leiomyosarcoma), and ESS-1 (endometrial stromal sarcoma) cell lines were used for the experiments. Cells were incubated in the presence of gemcitabine, fucoidan, and mixtures, after the incubation the MTT tests were performed. In order to assess the interactions between tested compounds isobolographic analysis was performed. Additional assessments of apoptosis and cell cycle were done. Results: Additive effect of combined treatment with gemcitabine and fucoidan was observed in ESS-1 and SK-UT-1 cell line. Although the supra-additive (synergistic) effect noticed in SK-UT-1B cell line. It was not possible to determine the interactions of fucoidan and gemcitabine in MES-SA cell line due to insuffcient response to treatment. Addition of fucoidan to gemcitabine enhances its proapoptotic activity, what was observed especially in ESS-1 and SK-UT-1B cell lines. The arrest of cell cycle induced by mixture of gemcitabine and fucoidan, superior comparing gemcitabine alone was observed in SK-UT-1B. Conclusions: Obtained data showed that a combination of fucoidan and gemcitabine in uterine endometrial stromal sarcoma and carcinosarcoma cell lines has additive or even synergistic effect in decreasing cell viability. Furthermore, this drug combination induces apoptosis and arrest of cell cycle. The resistance of uterine leiomyosarcoma cell line, justifies searching for other drugs combinations to improve therapy effcacyThe research was founded by Medical University of Lublin (grants No. DS 120, DS 121 and MNmd129)

Anticancer effect of ethanol <i>Lycium barbarum</i> (Goji berry) extract on human breast cancer T47D cell line

<p>The anticancer activity of ethanol extract isolated from Goji berry (EEGB) on T47D human breast cancer cell line has been reported. Cell viability and cell proliferation were examined with the use of BrdU, MTT and NR methods. Induction of apoptosis was assessed by propidium iodide and Hoechst 33342 staining. Expression of genes involved in cell proliferation, apoptosis, cell cycle control and regulation of transcription was estimated using Western blotting analysis. EEGB inhibited the proliferation of breast cancer cells in a time-, and dose-dependent manner. The study confirmed the lack of EEGB cytotoxic activity to normal human skin fibroblasts. Western blot analysis demonstrated an increase in pro-apoptotic and a decrease in anti-apoptotic proteins’ expression in cells treated with the extract. Anticancer activity and lack of toxicity against normal cells indicate a chemopreventive potential of Goji berries in breast cancer treatment.</p

Fucoidan Structure and Activity in Relation to Anti-Cancer Mechanisms

Fucoidan is a natural derived compound found in different species of brown algae and in some animals, that has gained attention for its anticancer properties. However, the exact mechanism of action is currently unknown. Therefore, this review will address fucoidans structure, the bioavailability, and all known different pathways affected by fucoidan, in order to formulate fucoidans structure and activity in relation to its anti-cancer mechanisms. The general bioactivity of fucoidan is difficult to establish due to factors like species-related structural diversity, growth conditions, and the extraction method. The main pathways influenced by fucoidan are the PI3K/AKT, the MAPK pathway, and the caspase pathway. PTEN seems to be important in the fucoidan-mediated effect on the AKT pathway. Furthermore, the interaction with VEGF, BMP, TGF-&beta;, and estrogen receptors are discussed. Also, fucoidan as an adjunct seems to have beneficial effects, for both the enhanced effectiveness of chemotherapy and reduced toxicity in healthy cells. In conclusion, the multipotent character of fucoidan is promising in future anti-cancer treatment. However, there is a need for more specified studies of the structure&ndash;activity relationship of fucoidan from the most promising seaweed species