The survival of patients with advanced or recurrent ovarian cancer has improved tremendously in the past decade, mainly due to the establishment of maintenance therapy with poly (ADP-ribose) polymerase (PARP) inhibitors (PARPis) after conservative chemotherapies. Despite their superior efficacy, resistance to PARPis has been reported, and patients with resistance have a much worse prognosis. Therefore, the development of novel treatment strategies to overcome PARPi resistance is urgently needed. The present review article focuses on the molecular mechanisms of how PARPis exert cytotoxic effects on cancer cells through DNA repair processes, especially the genetic background and tumor microenvironment favored by PARPis. Furthermore, currently available information on PARPi resistance mechanisms is introduced and discussed to develop a novel therapeutic approach against them.

Background: Since malignant struma ovarii is a very rare disease, its carcinogenic mechanism has not been elucidated. Here, we sought to identify the genetic lesions that may have led to the carcinogenesis of a rare case of malignant struma ovarii (follicular carcinoma) with peritoneal dissemination. Methods: DNA was extracted from the paraffin-embedded sections of normal uterine tissues and malignant struma ovarii for genetic analysis. Whole-exome sequencing and DNA methylation analysis were then performed. Results: Germline variants of RECQL4, CNTNAP2, and PRDM2, which are tumor-suppressor genes, were detected by whole-exome sequencing. Somatic uniparental disomy (UPD) was also observed in these three genes. Additionally, the methylation of FRMD6-AS2, SESN3, CYTL1, MIR4429, HIF3A, and ATP1B2, which are associated with tumor growth suppression, was detected by DNA methylation analysis. Conclusions: Somatic UPD and DNA methylation in tumor suppressor genes may be associated with the pathogenesis of malignant struma ovarii. To our knowledge, this is the first report of whole-exome sequencing and DNA methylation analysis in malignant struma ovarii. Genetic and DNA methylation analysis may help elucidate the mechanism of carcinogenesis in rare diseases and guide treatment decisions.

We have examined the performance of a see-through photovoltaics module that uses a low-concentration prism concentrator by undertaking ray-tracing analysis and an on-site experiment. The incident angle dependency of the prism concentrator makes it possible to concentrate direct solar radiation onto solar cells and transmit diffuse solar radiation. Fewer solar cells can then be used without sacrificing the conversion efficiency or lighting performance. The module generates approximately 1.15 more electricity than a conventional module while operating with 63% less solar cell area. We also introduce a design method for the concentrator geometry that adjusts the incident angle dependency for different latitude and tilt angles.

Endometriosis-harboring cancer-associated somatic mutations of PIK3CA and KRAS provides new opportunities for studying the multistep processes responsible for the functional and molecular changes in this disease. We aimed to establish a novel in vitro endometriosis model to clarify the functional behavior and molecular pathogenesis of this disorder. Immortalized HMOsisEC10 human ovarian endometriotic epithelial cell line was used in which KRAS and PIK3CA mutations were introduced. Migration, invasion, proliferation, and microarray analyses were performed using KRAS and PIK3CA mutant cell lines. In vitro assays showed that migration, invasion, and proliferation were significantly increased in KRAS and PIK3CA mutant cell lines, indicating that these mutations played causative roles in the aggressive behavior of endometriosis. Microarray analysis identified a cluster of gene signatures; among them, two significantly upregulated cancer-related genes, lysyl oxidase (LOX) and pentraxin3 (PTX3), were associated with cell proliferation, invasion, and migration capabilities. Furthermore, siRNA knockdown of the two genes markedly reduced the metastatic ability of the cells. These results suggest that endometriosis with KRAS or PIK3CA mutations can significantly enhance cell migration, invasion, and proliferation by upregulating LOX and PTX3. We propose that LOX and PTX3 silencing using small molecules could be an alternative therapeutic regimen for severe endometriosis.

Despite the knowledge about numerous genetic mutations essential for the progression of low-grade serous ovarian carcinoma (LGSOC), the specific combination of mutations required remains unclear. Here, we aimed to recognize the oncogenic mutations responsible for the stepwise development of LGSOC using immortalized HOVs-cyst-1 cells, developed from ovarian serous cystadenoma cells, and immortalized via cyclin D1, CDK4R24C, and hTERT gene transfection. Furthermore, oncogenic mutations, KRAS and PIK3CA, were individually and simultaneously introduced in immortalized HOV-cyst-1 cells. Cell functions were subsequently analyzed via in vitro assays. KRAS or PIK3CA double mutant HOV-cyst-1 cells exhibited higher cell proliferation and migration capacity than the wild-type cells, or those with either a KRAS or a PIK3CA mutation, indicating that these mutations play a causative role in LGSOC tumorigenesis. Moreover, KRAS and PIK3CA double mutants gained tumorigenic potential in nude mice, whereas the cells with a single mutant exhibited no signs of tumorigenicity. Furthermore, the transformation of HOV-cyst-1 cells with KRAS and PIK3CA mutants resulted in the development of tumors that were grossly and histologically similar to human LGSOCs. These findings suggest that simultaneous activation of the KRAS/ERK and PIK3CA/AKT signaling pathways is essential for LGSOC development.