Purpose: Developmentally regulated GTP-binding protein 2 (DRG2) regulates microtubule dynamics and G2/M arrest during docetaxel treatment. Poly ADP-ribose polymerase (PARP) acts as an important repair system for DNA damage caused by docetaxel treatment. This study investigated whether DRG2 expression affects response to PARP inhibitors (olaparib) using prostate cancer cell lines PC3, DU145, LNCaP-FGC, and LNCaP-LN3. Materials and Methods: The cell viability and DRG2 expression levels were assessed using colorimetric-based cell viability assay and western blot. Cells were transfected with DRG2 siRNA, and pcDNA6/V5-DRG2 was used to overexpress DRG2. Flow cytometry was applied for cell cycle assay and apoptosis analysis using the Annexing V cell death assay. Results: The expression of DRG2 was highest in LNCaP-LN3 and lowest in DU145 cells. Expressions of p53 in PC3, DU145, and the two LNCaP cell lines were null-type, high-expression, and medium-expression, respectively. In PC3 (DRG2 high, p53 null) cells, docetaxel increased G2/M arrest without apoptosis; however, subsequent treatment with olaparib promoted apoptosis. In DU145 and LNCaP-FGC (DRG2 low), docetaxel increased sub-G1 but not G2/M arrest and induced apoptosis, whereas olaparib had no additional effect. In LNCaP-LN3 (DRG2 high, p53 wild-type), docetaxel increased sub-G1 and G2/M arrest, furthermore olaparib enhanced cell death. Docetaxel and olaparib combination treatment had a slight effect on DRG2 knockdown PC3, but increased apoptosis in DRG2-overexpressed DU145 cells. Conclusions DRG2 and p53 expressions play an important role in prostate cancer cell lines treated with docetaxel, and DRG2 levels can predict the response to PARP inhibitors.

Transcription factor CP2-like protein 1 (Tfcp2l1), a naïve pluripotency transcription factor, is expressed in both early embryonic and adult tissues, where it enforces pluripotency of embryonic stem cells (ESCs) and stemness features of cancer cells, respectively. However, the detailed molecular pathways by which Tfcp2l1 is regulated in early embryonic development and cancer cells remain unknown. Here, we identified the pseudophosphatase dual specificity phosphatase 27 (Dusp27), also known as serine/threonine/tyrosine-interacting like-2, as a novel Tfcp2l1-interacting protein through a sterile alpha motif-like domain in the C-terminus of Tfcp2l1 in murine ESCs. The interaction between Dusp27 and Tfcp2l1 was dependent on the cell cycle status and increased during mitosis. Expression of Dusp27 was upregulated during naïve pluripotency and repressed during spontaneous differentiation of murine ESCs. Ectopic expression of Dusp27 enhanced the transcriptional activity of Tfcp2l1 and promoted features associated with the naïve pluripotent state, while suppressing meso-endodermal lineage differentiation. The present study demonstrates that Dusp27 is a novel positive regulator of Tfcp2l1 through a physical interaction and thereby fine-tunes the pluripotency status and meso-endodermal differentiation of murine ESCs.

Purpose: The cytotoxic T-lymphocyte-associated protein 4 (CTLA4) is involved in the progression of various cancers, but its biological roles in breast cancer (BRCA) remain unclear. Therefore, we performed a systematic multiomic analysis to expound on the prognostic value and underlying mechanism of CTLA4 in BRCA. Methods: We assessed the effect of CTLA4 expression on BRCA using a variety of bioinformatics platforms, including Oncomine, GEPIA, UALCAN, PrognoScan database, Kaplan-Meier plotter, and R2: Kaplan-Meier scanner. Results: CTLA4 was highly expressed in BRCA tumor tissue compared to normal tissue (P < 0.01). The CTLA4 messenger RNA levels in BRCA based on BRCA subtypes of Luminal, human epidermal growth factor receptor 2, and triple-negative BRCA were considerably higher than in normal tissues (P < 0.001). However, the overexpression of CTLA4 was associated with a better prognosis in BRCA (P < 0.001) and was correlated with clinicopathological characteristics including age, T stage, estrogen receptors, progesterone receptors, and prediction analysis of microarray 50 (P < 0.01). The infiltration of multiple immune cells was associated with increased CTLA4 expression in BRCA (P < 0.001). CTLA4 was highly enriched in antigen binding, immunoglobulin complexes, lymphocyte-mediated immunity, and cytokine-cytokine receptor interaction. Conclusion This study provides suggestive evidence of the prognostic role of CTLA4 in BRCA, which may be a therapeutic target for BRCA. Furthermore, CTLA4 may influence BRCA prognosis through antigen binding, immunoglobulin complexes, lymphocyte-mediated immunity, and cytokine-cytokine receptor interaction. These findings help us understand how CTLA4 plays a role in BRCA and set the stage for more research.

Background: In this study, we aimed to investigate whether opioid-sparing anesthesia (OSA) reduces postoperative nausea and vomiting (PONV) in patients undergoing laparoscopic gynecological surgery. Methods: Adult patients undergoing elective laparoscopic gynecological surgery were randomly assigned to either the opioid-using anesthesia (OUA) or the OSA groups. In the OUA group, remifentanil was administered as an opioid during general anesthesia. In the OSA group, apart from a single dose of 5 μg/kg of alfentanil for tracheal intubation, no other opioids were used. In both groups, a multimodal intravenous non-opioid analgesic regimen was used preferentially in the post-anesthesia care unit (PACU). The primary outcome was the incidence of PONV, assessed by symptoms until the postoperative day 1. Results: A total of 120 patients were included in this study. The incidence of nausea in the PACU was significantly lower in the OSA group compared to in the OUA group (31.7% in the OSA group vs. 51.7% in the OUA group, P = 0.026). Pain scores and the incidence of opioid analgesic administration were lower in the OSA group during PACU stay, resulting in a significantly lower number of patients requiring rescue opioid analgesics (3.3% vs. 18.3%, P = 0.008). There were no significant differences in intraoperative vital signs, hemodynamic interventions, or duration of PACU and hospital stay between the two groups. Conclusions OSA significantly reduced postoperative nausea, pain scores, and the need for rescue analgesics in the PACU without increasing hemodynamic instability in patients undergoing laparoscopic gynecological surgery.

Background: In this study, we aimed to investigate whether opioid-sparing anesthesia (OSA) reduces postoperative nausea and vomiting (PONV) in patients undergoing laparoscopic gynecological surgery. Methods: Adult patients undergoing elective laparoscopic gynecological surgery were randomly assigned to either the opioid-using anesthesia (OUA) or the OSA groups. In the OUA group, remifentanil was administered as an opioid during general anesthesia. In the OSA group, apart from a single dose of 5 μg/kg of alfentanil for tracheal intubation, no other opioids were used. In both groups, a multimodal intravenous non-opioid analgesic regimen was used preferentially in the post-anesthesia care unit (PACU). The primary outcome was the incidence of PONV, assessed by symptoms until the postoperative day 1. Results: A total of 120 patients were included in this study. The incidence of nausea in the PACU was significantly lower in the OSA group compared to in the OUA group (31.7% in the OSA group vs. 51.7% in the OUA group, P = 0.026). Pain scores and the incidence of opioid analgesic administration were lower in the OSA group during PACU stay, resulting in a significantly lower number of patients requiring rescue opioid analgesics (3.3% vs. 18.3%, P = 0.008). There were no significant differences in intraoperative vital signs, hemodynamic interventions, or duration of PACU and hospital stay between the two groups. Conclusions OSA significantly reduced postoperative nausea, pain scores, and the need for rescue analgesics in the PACU without increasing hemodynamic instability in patients undergoing laparoscopic gynecological surgery.