The differentiation properties of stem cells are not yet fully understood due to their close association with multiple environmental and extrinsic factors. This study investigates the differentiation properties of mesenchymal stem cells (MSCs) and correlates them with their intrinsic mechanical properties. A total of 3 different types of MSCs, namely bone marrow-derived MSCs (BMSCs), umbilical cord-derived MSCs (UCSCs), and adipose-derived MSCs (ADSCs) were evaluated. These 3 MSCs were individually differentiated into adipocytes and osteoblasts for 3 weeks. The mechanical properties of the MSCs and differentiated cells were determined by atomic force microscopy. ADSCs showed the greatest ability to differentiate into adipocytes, followed by BMSCs and UCSCs. While UCSCs differentiated readily into osteoblasts, BMSCs and ADSCs were less likely to undergo this differentiation. UCSCs were the "hardest" cells, while ADSCs were the "softest." The cells differentiated from "hard" MSCs were stiffer than the cells differentiated from "soft" MSCs, irrespective of lineage specification. The differentiation ability of MSCs and the mechanical properties of the differentiated cells were closely linked. However, there were no significant correlations regarding changes in the mechanical properties between the nuclear region and the cytoplasm during differentiation.

We evaluated the effect of red ginseng on toxicity, health-related quality of life (HRQL) and survival after adjuvant chemotherapy in patients with epithelial ovarian cancer (EOC). A total of 30 patients with EOC were randomly assigned to placebo (n = 15) and red ginseng groups (n = 15). All patients took placebo or red ginseng (3000 mg/day) for three months. Then, we compared changes of genotoxicity, HRQL and survival between the two groups. As a result, red ginseng reduced micronuclei yield in comparison with placebo despite no difference of binucleated cells index. Although red ginseng increased serum levels of alanine aminotransferase and aspartate aminotransferase significantly, they were within the normal value. Moreover, there were no differences in adverse events between placebo and red ginseng groups. In terms of HRQL, red ginseng was associated with improved emotional functioning and decreased symptoms of fatigue, nausea and vomiting, and dyspnea, reduced anxiety and interference affecting life and improved daytime somnolence. However, there was no effect of red ginseng on prognosis of EOC. Conclusively, red ginseng may be safe and effective to reduce genotoxicity and improve HRQL despite no benefit of survival in patients with EOC who received chemotherapy.

Shin KH, et al. Ann Lab Med. 2020 Jan;40(1):40-47. https://doi.org/10.3343/alm.2020.40.1.40

Perivascular epithelioid cell tumor (PEComa) is a rare subtype of mesenchymal origin tumor composed of epithelioid cells which exhibits immunohistochemical co-expressions of melanocytic markers and smooth muscle markers. In the first case, malignant uterine PEComa with vaginal and multiple lung metastasis was misdiagnosed preoperatively as uterine leiomyosarcoma despite a preoperative punch biopsy and immunohistochemical analysis of the metastatic vaginal mass. In the second case, synchronous uterine PEComa showing benign histology with lymph node involvement was incidentally detected after a staging operation for ovarian cancer. Definitive diagnosis of uterine PEComa was achieved only after hysterectomy despite preoperative assessment with pelvic magnetic resonance imaging and punch biopsy of metastatic lesion. The authors report two rare cases of uterine PEComa diagnosed postoperatively based on the morphologic and immunohistochemical features.

Ovarian cancer stem-like cells (CSCs) have been implicated in tumor recurrence, metastasis, and drug resistance. Accumulating evidence has demonstrated the antitumor effect of plasma-activated medium (PAM) in various carcinomas, including ovarian cancer. Thus, PAM represents a novel onco-therapeutic strategy. However, its impact on ovarian CSCs is unclear. Here, we show that ovarian CSCs resistant to high-dose conventional chemotherapeutic agents used for ovarian cancer treatment exhibited dose-dependent sensitivity to PAM. In addition, PAM treatment reduced the expression of stem cell markers and sphere formation, along with the aldehyde dehydrogenase- or CD133-positive cell population. We further investigated the effect of PAM in combination with other chemotherapeutics on ovarian CSCs in vitro. PAM exhibited synergistic cytotoxicity with cisplatin (CDDP) but not with paclitaxel and doxorubicin. In a peritoneal metastasis xenograft model established via intraperitoneal spheroid injection, PAM intraperitoneal therapy significantly suppressed peritoneal carcinomatosis (tumor size and number), with a more significant decrease observed due to the combined effects of PAM and CDDP with no side effects. Taken together, our results indicate that PAM inhibits ovarian CSC traits and exhibits synergetic cytotoxicity with CDDP, demonstrating PAM as a promising intraparietal chemotherapy for enhancing antitumor efficacy and reducing side effects.

Targeting the tumor vasculature is an attractive strategy for cancer treatment. However, the tumor vasculature is heterogeneous, and the mechanisms involved in the neovascularization of tumors are highly complex. Vasculogenic mimicry (VM) refers to the formation of vessel-like structures by tumor cells, which can contribute to tumor neovascularization, and is closely related to metastasis and a poor prognosis. Here, we report a novel function of AXL receptor tyrosine kinase (AXL) in the regulation of VM formation in breast cancer cells. MDA-MB-231 cells exhibited VM formation on Matrigel cultures, whereas MCF-7 cells did not. Moreover, AXL expression was positively correlated with VM formation. Pharmacological inhibition or AXL knockdown strongly suppressed VM formation in MDA-MB-231 cells, whereas the overexpression of AXL in MCF-7 cells promoted VM formation. In addition, AXL knockdown regulated epithelial–mesenchymal transition (EMT) features, increasing cell invasion and migration in MDA-MB-231 cells. Finally, the overexpression of microRNA-34a (miR-34a), which is a well-described EMT-inhibiting miRNA and targets AXL, inhibited VM formation, migration, and invasion in MDA-MB 231 cells. These results identify a miR-34a–AXL axis that is critical for the regulation of VM formation and may serve as a therapeutic target to inhibit tumor neovascularization.