Recent studies have demonstrated that the production of bidirectional enhancer-derived transcripts (eRNAs) is a characteristic of an active Cis-regulatory element (CRE). Higher levels of eRNA synthesis correlate with the activation of histone modifications, a potentially valuable tool for deciphering the complexity of the gene regulatory network. To understand the changes of CREs during gonadal development in mice, we collected gonadal WT1-positive cells from the piggyBac-Wt1-mCherry-2A-EGFP (PBWt1-RG) reporter strain at E13.5, E16.5, and P0 in both sexes and conducted Cap Analysis of Gene Expression analysis (CAGE) which is capable to capture transcriptional starting site (TSS). We compared the levels of intergenic bidirectional RNA, i.e, potentially eRNA, according to sex at each stage (testis somatic cells vs ovary somatic cells at E13.5, E16.5, and P0) and stage in each sex (E13.5 vs E16.5, E16.5 vs P0, and E13.5 vs P0 in testis somatic cells or ovary somatic cells). Intergenic RNAs with significant changes (|Log2FC| > 1, p < 0.05) were selected.The TSS profile of intergenic RNA changed more profoundly in testis somatic cells than in ovary somatic cells, suggesting embryonic testicular development is driven by larger changes in a transcriptional regulatory network than ovarian development. Based on the profiles of the predicted transcription factors (TFs) that would bind to the active CREs during gonadal development, the NR4A, EGR, and TCF3 families would be novel TFs to play pivotal roles in gonadal development. Identifying active CREs using eRNAs would provide a means to comprehensively understand the transcriptional regulatory system, leading to valuable insights into the gonadal development of male and female individuals.

Recent studies have demonstrated that the production of bidirectional enhancer-derived transcripts (eRNAs) is a characteristic of an active Cis-regulatory element (CRE). Higher levels of eRNA synthesis correlate with the activation of histone modifications, a potentially valuable tool for deciphering the complexity of the gene regulatory network. To understand the changes of CREs during gonadal development in mice, we collected gonadal WT1-positive cells from the piggyBac-Wt1-mCherry-2A-EGFP (PBWt1-RG) reporter strain at E13.5, E16.5, and P0 in both sexes and conducted Cap Analysis of Gene Expression analysis (CAGE) which is capable to capture transcriptional starting site (TSS). We compared the levels of intergenic bidirectional RNA, i.e, potentially eRNA, according to sex at each stage (testis somatic cells vs ovary somatic cells at E13.5, E16.5, and P0) and stage in each sex (E13.5 vs E16.5, E16.5 vs P0, and E13.5 vs P0 in testis somatic cells or ovary somatic cells). Intergenic RNAs with significant changes (|Log2FC| > 1, p < 0.05) were selected.The TSS profile of intergenic RNA changed more profoundly in testis somatic cells than in ovary somatic cells, suggesting embryonic testicular development is driven by larger changes in a transcriptional regulatory network than ovarian development. Based on the profiles of the predicted transcription factors (TFs) that would bind to the active CREs during gonadal development, the NR4A, EGR, and TCF3 families would be novel TFs to play pivotal roles in gonadal development. Identifying active CREs using eRNAs would provide a means to comprehensively understand the transcriptional regulatory system, leading to valuable insights into the gonadal development of male and female individuals.

Background: Fruquintinib is a selective vascular endothelial growth factor receptor (VEGFR) inhibitor approved for metastatic colorectal cancer (mCRC) that is refractory to standard therapies. While its efficacy and safety have been demonstrated in phase III trials, data on its use in patients undergoing hemodialysis for end-stage renal disease (ESRD) are lacking. We report the first known case of fruquintinib administration in a patient undergoing maintenance hemodialysis.Case Presentation: A 66-year-old woman with mCRC and ESRD undergoing thrice-weekly hemodialysis received multiple lines of chemotherapy, including FOLFOX, FOLFIRI, and regorafenib. Owing to progressive disease and limited treatment options, fruquintinib was initiated after informed consent was obtained. The starting dose was 3 mg/day, with escalation to 4 mg, and subsequently to 5 mg in later cycles. The drug was administered daily regardless of the dialysis schedule. Adverse events, graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, included Grade 1 fatigue and diarrhea and Grade 3 anemia requiring transfusion, which was attributed to underlying renal anemia rather than fruquintinib. Clinically significant hypertension, electrolyte disturbances, or other toxicities were not observed. Despite acceptable tolerability, computed tomography (CT) after three cycles indicated disease progression.Conclusion: This case suggests that fruquintinib may be administered safely to selected patients with mCRC on maintenance hemodialysis. Further data are needed to establish dosing strategies and monitor potential toxicities in this population.

Background: Fruquintinib is a selective vascular endothelial growth factor receptor (VEGFR) inhibitor approved for metastatic colorectal cancer (mCRC) that is refractory to standard therapies. While its efficacy and safety have been demonstrated in phase III trials, data on its use in patients undergoing hemodialysis for end-stage renal disease (ESRD) are lacking. We report the first known case of fruquintinib administration in a patient undergoing maintenance hemodialysis.Case Presentation: A 66-year-old woman with mCRC and ESRD undergoing thrice-weekly hemodialysis received multiple lines of chemotherapy, including FOLFOX, FOLFIRI, and regorafenib. Owing to progressive disease and limited treatment options, fruquintinib was initiated after informed consent was obtained. The starting dose was 3 mg/day, with escalation to 4 mg, and subsequently to 5 mg in later cycles. The drug was administered daily regardless of the dialysis schedule. Adverse events, graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, included Grade 1 fatigue and diarrhea and Grade 3 anemia requiring transfusion, which was attributed to underlying renal anemia rather than fruquintinib. Clinically significant hypertension, electrolyte disturbances, or other toxicities were not observed. Despite acceptable tolerability, computed tomography (CT) after three cycles indicated disease progression.Conclusion: This case suggests that fruquintinib may be administered safely to selected patients with mCRC on maintenance hemodialysis. Further data are needed to establish dosing strategies and monitor potential toxicities in this population.