Purpose To assess the effectiveness and safety of percutaneous computed tomography (CT)-guided radiofrequency ablation (RFA) for lymph node (LN) oligometastases from hepatocellular carcinoma (HCC). Materials and Methods This retrospective study was approved by the institutional ethics committee, and all patients provided written informed consent. From January 2004 to December 2013, 119 consecutive patients with HCC and LN oligometastases (115 men [mean age, 51.3 years; age range, 16-83 years] and four women [mean age, 38.2 years; age range, 23-47 years]) were included in this study. A matched cohort composed of 46 patients from each group was selected after adjustment with propensity score matching. The median follow-up time was 14.0 months in the RFA group and 13.8 months in the non-RFA group. The overall survival (OS), local control rate, and complications were evaluated. Survival curves were constructed with the Kaplan-Meier method and compared by using the log-rank test. Results Eighty-seven patients had LN metastases located in the regional site, and 32 patients had LN metastases in the distant site. No significant differences were observed in the baseline characteristics between groups after propensity score matching adjustment. The RFA group showed higher 6-month and 1-year OS rates compared with the non-RFA group (87.0% and 58.3% vs 62.4% and 17.9%, respectively; P = .001). The 3-month local control rate after RFA was 84.4%, including complete response in 71.1% of patients and partial response in 13.3%. The complications of RFA were short-term abdominal pain and self-limited local hematoma, which occurred in 10 patients (21.7%) and five patients (10.9%), respectively. Conclusion Percutaneous CT-guided RFA may be a safe and effective treatment for the LN oligometastases generated by HCC. RSNA, 2016.

Background Ovarian follicles, which are the basic units of female reproduction, are composed of oocytes and surrounding somatic (pre) granulosa cells (GCs). A recent study revealed that signaling in somatic preGCs controlled the activation (initial recruitment) of follicles in the adult ovaries, but it is also known that there are two waves of follicle with age-related heterogeneity in their developmental dynamics in mammals. Although this heterogeneity was proposed to be crucial for female reproduction, our understanding of how it arises and its significance is still elusive. Results In the current study, by deleting the key secreted factor KIT ligand from preGCs and analyzing the follicle cell developmental dynamics, we revealed distinct patterns of activation and growth associated with the two waves of follicles in mouse ovary. Our results confirmed that activation of adult wave follicles is initiated by somatic preGCs and dependent on the KIT ligand. By contrast, activation of first wave follicles, which are awakened from germ cells before follicle formation, can occur in the absence of preGC-secreted KIT ligand in postnatal ovaries and appears to be oocyte-initiated. We also found that the asynchronous activity of phosphatidylinositol 3 kinases (PI3K) signaling and meiotic process in embryonic germ cells lead to the follicle heterogeneity in postnatal ovaries. In addition, we supplied evidence that the time sequence of embryonic germ cell development and its related first wave follicle growth are correlated to the time of puberty onset in females. Conclusion Taken together, our study provides evidence that asynchronous development of embryonic oocytes leads to the heterogeneity of postnatal ovarian follicle activation and development, and affects the timing of onset of puberty in females.

Unique model of adult ovarian angiogenesis implies a strategy to extend female reproductive life span.

We established an efficient and simplified single-cell proteomics (ES−SCP) workflow to realize proteomics profiling at the single-oocyte level. With the ES−SCP workflow, we constructed a deep coverage proteome library during oocyte maturation, which contained more than 6000 protein groups, and identified and quantified more than 4000 protein groups from a pool of only 15 oocytes at germinal vesicle (GV), GV breakdown (GVBD), and metaphase II (MII) stages. More than 1500 protein groups can be identified from single oocytes. We found that marker proteins including maternal factors and mRNA regulators, such as ZAR1, TLE6, and BTG4, showed significant variations in abundance during oocyte maturation, and it was discovered that maternal mRNA degradation was indispensable during oocyte maturation. Proteomics analysis from single oocytes revealed that changes in antioxidant factors, maternal factors, mRNA stabilization, and energy metabolism were the factors that affect the oocyte quality during ovary aging. Our data laid the foundation for future innovations in assisted reproduction.

Ovarian granulosa cell tumors (GCTs) originate from granulosa cells (GCs) and represent the most common sex cord-stromal tumor in humans. However, the developmental regulations and molecular mechanisms underlying their etiology are largely unknown. In the current study, we combined a multi-fluorescent reporter mouse model with a conditional knockout mouse model, in which the tumor suppressor genes Pten and p27 were deleted in GCs, to perform cell lineage tracing of mutant GCs. We found that only 30% of ovaries with substantial mutant GCs developed into GCTs that derived from a single mutant GC. In-depth molecular analysis of the process of tumorigenesis demonstrated that up-regulation of immune evasion genes Cd24a and Cd47 led, in part, to the transition of mutant GCs to GCTs. Therefore, treatment with the Cd47 inhibitor RRX-001 was tested and found to efficiently suppress the growth of GCTs in vivo. Together, our study has revealed an immune evasion mechanism via CD24/CD47 upregulation to GCT formation, shedding light on the future potential clinical therapies for GCTs.