Cell size homeostasis is a conserved attribute in many eukaryotic species involving a tight regulation between the processes of growth and proliferation. In budding yeast S. cerevisiae, growth to a “critical cell size” must be achieved before a cell can progress past START and commit to cell division. Numerous studies have shown that progression past START is actively regulated by cell size control genes, many of which have implications in cell cycle control and cancer. Two initial screens identified genes that strongly modulate cell size in yeast. Since a second generation yeast gene knockout collection has been generated, we screened an additional 779 yeast knockouts containing 435 new ORFs (~7% of the yeast genome) to supplement previous cell size screens. Upon completion, 10 new strong size mutants were identified: nine in log-phase cells and one in saturation-phase cells, and 97% of the yeast genome has now been screened for cell size mutations. The majority of the logarithmic phase size mutants have functions associated with translation further implicating the central role of growth control in the cell division process. Genetic analyses suggest ECM9 is directly associated with the START transition. Further, the small (whi) mutants mrpl49Δ and cbs1Δ are dependent on CLN3 for cell size effects. In depth analyses of new size mutants may facilitate a better understanding of the processes that govern cell size homeostasis.

Ovarian cancer is the deadliest gynecologic malignancy, accounting for more than 14,000 deaths each year. With no established way to prevent or screen for it, the vast majority of cases are diagnosed as International Federation of Gynecology and Obstetrics (FIGO) stage III or higher. Individuals with germline BRCA mutations are at particularly high risk for epithelial ovarian cancer and have been the subject of many risk-reducing strategies. In the past ten years, studies looking at risk-reducing salpingo-oophorectomy (RRSO) in this population have uncovered an interesting association: up to 8% of women with BRCA1 or BRCA2 mutations who underwent RRSO had an associated serous tubal intraepithelial carcinoma (STIC). The importance of this finding is highlighted by the fact that up to 60% of ovarian cancer patients will also have an associated STIC. These studies have led to a paradigm shift that a subset of epithelial ovarian cancer originates not in the ovarian epithelium, but rather in the distal fallopian tube. In response to this, many providers have changed their practice by expanding the role of routine salpingectomy, hysterectomy, and sterilization procedures. The American College of Obstetricians and Gynecologists (ACOG) has acknowledged opportunistic salpingectomy as a safe strategy to reduce the risk of epithelial ovarian cancer in Committee Opinion #774. It is thus important for pathologists and clinicians to understand the definition of STIC; how it is diagnosed; and, most importantly, its clinical significance.

Background: Ovarian cancer is the deadliest gynecologic malignancy despite current first-line treatment with a platinum and taxane doublet. Artesunate has broad antineoplastic properties but has not been investigated in combination with carboplatin and paclitaxel for ovarian cancer treatment. Methods: Standard cell culture technique with commercially available ovarian cancer cell lines were utilized in cell viability, DNA damage, and cell cycle progression assays to qualify and quantify artesunate treatment effects. Additionally, the sequence of administering artesunate in combination with paclitaxel and carboplatin was determined. The activity of artesunate was also assessed in 3D organoid models of primary ovarian cancer and RNAseq analysis was utilized to identify genes and the associated genetic pathways that were differentially regulated in artesunate resistant organoid models compared to organoids that were sensitive to artesunate. Results: Artesunate treatment reduces cell viability in 2D and 3D ovarian cancer cell models. Clinically relevant concentrations of artesunate induce G1 arrest, but do not induce DNA damage. Pathways related to cell cycle progression, specifically G1/S transition, are upregulated in ovarian organoid models that are innately more resistant to artesunate compared to more sensitive models. Depending on the sequence of administration, the addition of artesunate to carboplatin and paclitaxel improves their effectiveness. Conclusions: Artesunate has preclinical activity in ovarian cancer that merits further investigation to treat ovarian cancer.

Background: Ovarian cancer (OC) is the leading cause of death from gynecologic malignancy and is treated with a combination of cytoreductive surgery and platinum-based chemotherapy. Extended length of stay (LOS) after surgery can affect patient morbidity, overall costs, and hospital resource utilization. The primary objective of this study was to identify factors contributing to prolonged LOS for women undergoing surgery for ovarian cancer. Methods: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was queried to identify women from 2012–2016 who underwent hysterectomy for ovarian, fallopian tube and peritoneal cancer. The primary outcome was LOS >50th percentile. Preoperative and intraoperative variables were examined to determine which were associated with prolonged LOS. Results: From 2012–2016, 1771 women underwent elective abdominal surgery for OC and were entered in the ACS-NSQIP database. The mean and median LOS was 4.6 and 4.0 days (IQR 0–38), respectively. On multivariate analysis, factors associated with prolonged LOS included: American Society of Anesthesiologists (ASA) Classification III (aOR 1.71, 95% CI 1.38–2.13) or IV (aOR 1.88, 95% CI 1.44–2.46), presence of ascites (aOR 1.88, 95% CI 1.44–2.46), older age (aOR 1.23, 95% CI 1.13–1.35), platelet count >400,000/mm3 (aOR 1.74, 95% CI 1.29–2.35), preoperative blood transfusion (aOR 11.00, 95% CI 1.28–94.77), disseminated cancer (aOR 1.28, 95% CI 1.03–1.60), increased length of operation (121–180 min, aOR 1.47, 95% CI 1.13-1.91; >180 min, aOR 2.78, 95% CI 2.13–3.64), and postoperative blood transfusion within 72 h of incision (aOR 2.04, 95% CI 1.59–2.62) (p < 0.05 for all). Conclusions: Longer length of hospital stay following surgery for OC is associated with many patient, disease, and treatment-related factors. The extent of surgery, as evidenced by perioperative blood transfusion and length of surgical procedure, is a factor that can potentially be modified to shorten LOS, improve patient outcomes, and reduce hospital costs.