Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy and has a unique metastatic route using ascites, known as the transcoelomic root. However, studies on ascites and contained cellular components have not yet been sufficiently clarified. In this review, we focus on the significance of accumulating ascites, contained EOC cells in the form of spheroids, and interaction with non-malignant host cells. To become resistant against anoikis, EOC cells form spheroids in ascites, where epithelial-to-mesenchymal transition stimulated by transforming growth factor-β can be a key pathway. As spheroids form, EOC cells are also gaining the ability to attach and invade the peritoneum to induce intraperitoneal metastasis, as well as resistance to conventional chemotherapy. Recently, accumulating evidence suggests that EOC spheroids in ascites are composed of not only cancer cells, but also non-malignant cells existing with higher abundance than EOC cells in ascites, including macrophages, mesothelial cells, and lymphocytes. Moreover, hetero-cellular spheroids are demonstrated to form more aggregated spheroids and have higher adhesion ability for the mesothelial layer. To improve the poor prognosis, we need to elucidate the mechanisms of spheroid formation and interactions with non-malignant cells in ascites that are a unique tumor microenvironment for EOC.

Ovarian cancer has one of the poorest prognoses among carcinomas. Advanced ovarian cancer often develops ascites and peritoneal dissemination, which is one of the poor prognostic factors. From the perspective of the “seed and soil” hypothesis, the intra-abdominal environment is like the soil for the growth of ovarian cancer (OvCa) and mesothelial cells (MCs) line the top layer of this soil. In recent years, various functions of MCs have been reported, including supporting cancer in the OvCa microenvironment. We refer to OvCa-associated MCs (OCAMs) as MCs that are stimulated by OvCa and contribute to its progression. OCAMs promote OvCa cell adhesion to the peritoneum, invasion, and metastasis. Elucidation of these functions may lead to the identification of novel therapeutic targets that can delay OvCa progression, which is difficult to cure.

Patients with Wilms tumor (WT) in general have excellent survival, but the prognosis of patients belonging to the subgroup of WT with diffuse anaplasia (DA) is poor due to frequent resistance to chemotherapy. We hypothesized that DA WT cells might undergo changes, such as acquiring a persistent tolerance to DNA damage and copy number aberrations (CNAs), which could eventually lead to their resistance to chemotherapy treatment. Tissue sections from chemotherapy-treated DA WTs (n = 12) were compared with chemotherapy-treated nonanaplastic WTs (n = 15) in a tissue microarray system, enabling analysis of 769 tumor regions. All regions were scored for anaplastic features and immunohistochemistry was used to quantify p53 expression, proliferation index (Ki67), and DNA double-strand breaks (γH2AX). CNAs were assessed by array-based genotyping and TP53 mutations using targeted sequencing. Proliferation index and the frequency of DNA double-strand breaks (γH2AX dot expression) increased with higher anaplasia scores. Almost all (95.6%) areas with full-scale anaplasia had TP53 mutations or loss of heterozygosity, along with an increased amount of CNAs. Interestingly, areas with wild-type TP53 with loss of heterozygosity and only one feature of anaplasia (anaplasia score 1) also had significantly higher proliferation indices, more DNA double-strand breaks, and more CNAs than regions without any anaplastic features (score 0); such areas may be preanaplastic cell populations under selective pressure for TP53 mutations. In conclusion, we suggest that chemoresistance of DA WTs may be partly explained by a high proliferative capability of anaplastic cells, which also have a high burden of double-stranded DNA breaks and CNAs, and that there is a gradual emergence of anaplasia in WT.

Large cardiac rhabdomyomas can disturb hemodynamic flow. Tuberous sclerosis complex is the most common cause of cardiac rhabdomyoma in fetuses. Recently, a mammalian target of rapamycin (mTOR) inhibitor effectively treated rhabdomyomas associated with tuberous sclerosis. Here, we report the effectiveness of an mTOR inhibitor in treating a fetus with large rhabdomyomas exhibiting severe heart failure when administered transplacentally. A 30-year-old pregnant woman was transferred to our hospital due to the presence of a cardiac tumor in the left ventricle (LV) of the fetus, which gradually enlarged to > 40 mm in diameter. The diastolic and systolic functions of the LV were completely disrupted. At 32 weeks of gestation, the fetus showed severe heart failure (cardiovascular profile score 7), with a high risk of death. The hemodynamic flow was consistent with hypoplastic left heart syndrome. Fetal magnetic resonance imaging revealed several cranial regions with 7.9 × 6.9 mm subependymal giant cell astrocytoma (SEGA). The fetus was clinically diagnosed with tuberous sclerosis, and therapy was initiated with maternally administered sirolimus, an mTOR inhibitor. Sirolimus effectively reduced the size of the tumor and improved the hemodynamics of the fetus. No severe complications occurred in the mother or fetus. The baby was born at 39 weeks of gestation with a mildly reduced LV ejection fraction. In addition, the dimensions of the intracranial SEGA decreased somewhat following initiation of maternal sirolimus treatment. Postnatal genetic testing confirmed a mutation in the TSC2 gene. Currently, the baby is 3 months old with normal neurological development. Transplacental sirolimus administration can be a useful in treating large rhabdomyomas that disturb fetal hemodynamics.