Supplementary Material for: Activation of the GPR30 Receptor Promotes Lordosis in Female Mice

<b><i>Background/Aims:</i></b> Estrogens are important effectors of reproduction and are critical for upregulating female reproductive behavior or lordosis in females. In addition to the importance of transcriptional regulation of genes by 17β-estradiol-bound estrogen receptors (ER), extranuclear signal transduction cascades such as protein kinase A (PKA) are also important in regulating female sexual receptivity. GPR30 (G-protein coupled receptor 30), also known as GPER1, a putative membrane ER (mER), is a G protein-coupled receptor that binds 17β-estradiol with an affinity that is similar to that possessed by the classical nuclear ER and activates both PKA and extracellular-regulated kinase signaling pathways. The high expression of GPR30 in the ventromedial hypothalamus, a region important for lordosis behavior as well as kinase cascades activated by this receptor, led us to hypothesize that GPR30 may regulate lordosis behavior in female rodents. <b><i>Method:</i></b> In this study, we investigated the ability of G-1, a selective agonist of GPR30, to regulate lordosis in the female mouse by administering this agent prior to progesterone in an estradiol-progesterone priming paradigm prior to testing with stud males. <b><i>Results:</i></b> As expected, 17β-estradiol benzoate (EB), but not sesame oil, increased lordosis behavior in female mice. G-1 also increased lordosis behavior in female mice and decreased the number of rejective responses towards male mice, similar to the effect of EB. The selective GPR30 antagonist G-15 blocked these effects. <b><i>Conclusion:</i></b> This study demonstrates that activation of the mER GPR30 stimulates social behavior in a rodent model in a manner similar to EB

Supplementary Material for: Venetoclax–azacitidine bridging PTCy-haplo-PBSCT for refractory acute myeloid leukemia with IDH2 mutations

Venetoclax and azacitidine combination therapy (VEN+AZA) is a promising novel therapy for elderly or unfit patients with acute myeloid leukemia (AML). Recently, VEN+AZA with subsequent allo-hematopoietic stem cell transplantation (allo-HSCT) has been reported, and human leukocyte antigen (HLA)-haploidentical peripheral blood stem cell transplantation using post-transplant cyclophosphamide (PTCy-haplo-PBSCT) from related donors appears to be a suitable option. Here, we report two elderly patients with refractory AML harboring an IDH2 mutation, which was successfully treated with VEN+AZA bridged to PTCy-haplo-PBSCT. This report suggests the efficacy and safety of VEN+AZA as a bridging treatment for PTCy-haplo-PBSCT in refractory AML

Supplementary Material for: Serum angiopoietin-2 levels predict the development of hepatocellular carcinoma following hepatitis C virus eradication using direct-acting antiviral agents

Introduction: Our previous studies showed that serum angiopoietin-2 (Ang-2) and C-X-C motif chemokine ligand 10 (CXCL10) levels predicted improvement in liver fibrosis following sustained virological response (SVR) of hepatitis C virus (HCV) obtained with administration of with direct-acting antiviral agents (DAAs). These levels were evaluated retrospectively as predictive indicators of hepatocellular carcinoma (HCC) development following SVR. Methods: We enrolled individuals from a historical cohort of 89 chronic HCV patients without history of HCC at baseline and with SVR following DAA therapy and had baseline serum levels of Mac-2 binding protein glycosylation isomer ≥ 2.0 C.O.I. Results: Multivariate analyses revealed that only the Ang-2 level at 24 weeks following the end of treatment (EOT24W) was significantly related to HCC development (hazard ratio 2.27; P = 0.003). This result was reproduced in individuals without history of HCC and with advanced liver fibrosis (M2BPGi level ≥ 3.3 C.O.I. at baseline). Time-dependent receiver operating characteristic curve analyses for the future risk of developing HCC within 5 years of follow-up (5y-HCC) showed the best cut-off Ang-2 level at the EOT24W was 2,780 pg/mL, and significantly stratified the cumulative incidence of HCC (≥ 2,780 vs. < 2,780 pg/mL, 5y-HCC: 45.5 vs. 8.2%, P < 0.001). Conclusions: At the EOT24W, serum Ang-2 level predicts the likelihood of developing HCC following SVR to DAA therapy

Supplementary Material for: Serum angiopoietin-2 levels predict the development of hepatocellular carcinoma following hepatitis C virus eradication using direct-acting antiviral agents

Introduction: Our previous studies showed that serum angiopoietin-2 (Ang-2) and C-X-C motif chemokine ligand 10 (CXCL10) levels predicted improvement in liver fibrosis following sustained virological response (SVR) of hepatitis C virus (HCV) obtained with administration of with direct-acting antiviral agents (DAAs). These levels were evaluated retrospectively as predictive indicators of hepatocellular carcinoma (HCC) development following SVR. Methods: We enrolled individuals from a historical cohort of 89 chronic HCV patients without history of HCC at baseline and with SVR following DAA therapy and had baseline serum levels of Mac-2 binding protein glycosylation isomer ≥ 2.0 C.O.I. Results: Multivariate analyses revealed that only the Ang-2 level at 24 weeks following the end of treatment (EOT24W) was significantly related to HCC development (hazard ratio 2.27; P = 0.003). This result was reproduced in individuals without history of HCC and with advanced liver fibrosis (M2BPGi level ≥ 3.3 C.O.I. at baseline). Time-dependent receiver operating characteristic curve analyses for the future risk of developing HCC within 5 years of follow-up (5y-HCC) showed the best cut-off Ang-2 level at the EOT24W was 2,780 pg/mL, and significantly stratified the cumulative incidence of HCC (≥ 2,780 vs. < 2,780 pg/mL, 5y-HCC: 45.5 vs. 8.2%, P < 0.001). Conclusions: At the EOT24W, serum Ang-2 level predicts the likelihood of developing HCC following SVR to DAA therapy