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Objective: Octamer transcription factor 1 (OCT1), a transcription factor that interacts with androgen receptor, is involved in prostate cancer (PCa) progression. The OCT1 target gene, Anillin actin-binding protein ( ANLN ), is highly expressed in castration-resistant PCa tissue; however, it remains unclear whether ANLN expression in hormone-sensitive PCa tissue could be used as a predictive biomarker for poor prognosis of patients. We aimed to investigate ANLN expression in PCa tissue obtained via radical prostatectomy and its correlation with clinical parameters., Methods: Immunohistochemical staining for ANLN was performed on 86 PCa specimens, followed by evaluation using immunoreactivity (IR) scores. Prognosis was analyzed by the log-rank test using the Kaplan-Meier method to generate a cancer-specific survival curve. The correlations between ANLN IR and clinical parameters as well as OCT1 IR were analyzed using the Chi-squared test., Results: The median IR score was 0 for ANLN. Accordingly, given the low median IR score, an IR score of ≥3 was defined as positive. There were 17 (19.8%) ANLN-positive cases, and these cases had a significantly poorer prognosis. Multivariate analysis revealed that the Gleason score, pathological tumor and lymph node stages, and positive ANLN expression were significant predictors of poor prognosis. Notably, patients with both positive ANLN and high OCT1 expression had a significantly decreased overall survival ( p =0.001)., Conclusion: ANLN , which is a OCT1 target gene especially in castration-resistant PCa, is expressed in a small number of hormone-sensitive PCa cases. Both positive ANLN expression and high OCT1 expression are significantly correlated with poor prognosis for PCa patients., Competing Interests: The authors declare no conflict of interest., (© 2024 Editorial Office of Asian Journal of Urology. Production and hosting by Elsevier B.V.)

Background: Prostate cancer is dependent on androgen receptor (AR) signaling, and androgen deprivation therapy (ADT) has proven effective in targeting prostate cancer. However, castration-resistant prostate cancer (CRPC) eventually emerges. AR signaling inhibitors (ARSI) have been also used, but resistance to these agents develops due to genetic AR alterations and epigenetic dysregulation., Methods: In this study, we investigated the role of OCT1, a member of the OCT family, in an AR-positive CRPC patient-derived xenograft established from a patient with resistance to ARSI and chemotherapy. We conducted a genome-wide analysis chromatin immunoprecipitation followed by sequencing and bioinformatic analyses using public database., Results: Genome-wide analysis of OCT1 target genes in PDX 201.1 A revealed distinct OCT1 binding sites compared to treatment-naïve cells. Bioinformatic analyses revealed that OCT1-regulated genes were associated with cell migration and immune system regulation. In particular, C-terminal Binding Protein 2 (CTBP2), an OCT1/AR target gene, was correlated with poor prognosis and immunosuppressive effects in the tumor microenvironment. Metascape revealed that CTBP2 knockdown affects genes related to the immune response to bacteria. Furthermore, TISIDB analysis suggested the relationship between CTBP2 expression and immune cell infiltration in prostate cancer, suggesting that it may contribute to immune evasion in CRPC., Conclusions: Our findings shed light on the genome-wide network of OCT1 and AR in AR-positive CRPC and highlight the potential role of CTBP2 in immune response and tumor progression. Targeting CTBP2 may represent a promising therapeutic approach for aggressive AR-positive CRPC. Further validation will be required to explore novel therapeutic strategies for CRPC management., (© 2024. The Author(s).)

This study investigated the effects of timed artificial insemination (TAI) and equine chorionic gonadotropin (eCG) administration on lactating dairy cows under heat-stress conditions (average temperature-humidity index: 80). Timed artificial insemination was performed on the cows with (n = 57) or without (control, n = 41) supplementation with 500 IU of eCG at the day of PGF 2α treatment using the CIDR-Ovsynch protocol. GnRH was administered, and a progesterone device (CIDR) was inserted on Day -10 of the treatment protocol. The CIDR was removed on Day -3, and the cows were treated with PGF 2α . Two days later, a 2 nd GnRH injection was administered. Subsequently, AI was performed on Day 0 (16-20 h after the 2 nd GnRH injection), and pregnancy was diagnosed on Days 32 and 60. Plasma progesterone (P 4 ) concentrations were measured after AI. Results showed that the eCG group had a higher pregnancy per AI (P/AI) than the control group (43.9 vs. 12.2%, P = 0.002), which was also accompanied by elevated P 4 levels. Four cows in the eCG group had multiple calves, representing 7.0 and 16.0% of the group and pregnant cows, respectively. In conclusion, 500 IU of eCG combined with CIDR-Ovsynch in lactating dairy cows under severe heat stress conditions successfully improved fertility. However, the protocol may have a slight risk of multiple births.

Androgens and androgen receptor (AR) have a central role in prostate cancer progression by regulating its downstream signaling. Although androgen depletion therapy (ADT) is the primary treatment for most prostate cancers, they acquires resistance to ADT and become castration resistant prostate cancers (CRPC). AR complex formation with multiple transcription factors is important for enhancer activity and transcriptional regulation, which can contribute to cancer progression and resistance to ADT. We previously demonstrated that OCT1 collaborates with AR in prostate cancer, and that a pyrrole-imidazole (PI) polyamide (PIP) targeting OCT1 inhibits cell and castration-resistant tumor growth (Obinata D et al. Oncogene 2016). PIP can bind to DNA non-covalently without a drug delivery system unlike most DNA targeted therapeutics. In the present study, we developed a PIP modified with a DNA alkylating agent, chlorambucil (ChB) (OCT1-PIP-ChB). Then its effect on the growth of prostate cancer LNCaP, 22Rv1, and PC3 cells, pancreatic cancer BxPC3 cells, and colon cancer HCT116 cells, as well as non-cancerous MCF-10A epithelial cells, were analyzed. It was shown that the IC50s of OCT1-PIP-ChB for 22Rv1 and LNCaP were markedly lower compared to other cells, including non-cancerous MCF-10A cells. Comprehensive gene expression analysis of CRPC model 22Rv1 cells treated with IC50 concentrations of OCT1-PIP-ChB revealed that the gene group involved in DNA double-strand break repair was the most enriched among gene sets repressed by OCT1-PIP-ChB treatment. Importantly, in vivo study using 22Rv1 xenografts, we showed that OCT1-PIP-ChB significantly reduced tumor growth compared to the control group without showing obvious adverse effects. Thus, the PIP combined with ChB can exert a significant inhibitory effect on prostate cancer cell proliferation and castration-resistant tumor growth, suggesting a potential role as a therapeutic agent., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

This study aimed to clarify the real-world efficacy of sequential nivolumab for treating metastatic renal cancer after first-line molecular targeting therapy. Patients were divided into two groups (2014-2016 and 2017-2020) according to the year when they started primary treatment with molecular targeted drugs (MTDs). We compared the overall survival of patients and investigated a contributing factor for survival. The mean duration of overall survival was significantly longer in the 2017-2020 group (44.0 months) than in the 2014-2016 group (8.5 months). Univariate analysis showed that nivolumab treatment was a significant prognostic factor (P = .0021). Patients treated with nivolumab as second-line therapy had a significantly higher 5-year survival rate compared to that of other patients (70% vs 32%). In addition, the time from commencement of MTDs to switch to nivolumab was significantly shorter in the 2017-2020 group compared to the 2014-2016 group (8.94 vs 34.12 months, P = .03). In our study, cases with first-line MTDs had markedly prolonged outcomes after the 2017 guideline update, and sequential nivolumab with prompt switching to nivolumab was an important factor., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Androgen and androgen receptor (AR) targeted therapies are the main treatment for most prostate cancer (PC) patients. Although AR signaling inhibitors are effective, tumors can evade this treatment by transforming to an AR-negative PC via lineage plasticity. OCT1 is a transcription factor interacting with the AR to enhance signaling pathways involved in PC progression, but its role in the emergence of the AR-negative PC is unknown. We performed chromatin immunoprecipitation sequencing (ChIP-seq) in patient-derived castration-resistant AR-negative PC cells to identify genes that are regulated by OCT1. Interestingly, a group of genes associated with neural precursor cell proliferation was significantly enriched. Then, we focused on neural genes STNB1 and PFN2 as OCT1-targets among them. Immunohistochemistry revealed that both STNB1 and PFN2 are highly expressed in human AR-negative PC tissues. Knockdown of SNTB1 and PFN2 by siRNAs significantly inhibited migration of AR-negative PC cells. Notably, knockdown of PFN2 showed a marked inhibitory effect on tumor growth in vivo. Thus, we identified OCT1-target genes in AR-negative PC using a patient-derived model, clinicopathologial analysis and an animal model., (© 2022. The Author(s).)

Objective: To compare the surgical outcomes of laparoscopic sacrocolpopexy for pelvic organ prolapse between a group in which only sutures were used (standard method), and a group in which a combination of tackers and sutures were used (tacker combination method)., Methods: A total of 77 patients who underwent laparoscopic sacrocolpopexys from June 2016 to October 2019 were divided into a suture group (36 patients) and a suture + tacker group (41 patients). We retrospectively compared operation time, amount of blood loss, postoperative length of hospital stay, incidence of perioperative complications and anatomical cure rate 1 year after surgery. Lower urinary tract symptoms were evaluated using symptom questionnaires and objective parameters., Results: Operation time in the suture + tacker group was shorter (104.9 ± 27.0 vs 147.5 ± 33.7 min; P < 0.0001). The incidence of perioperative complications in the suture group and the suture + tacker group was 2.8% and 2.4%, respectively (P = 0.9409). Anatomical cure rates at 1 year after surgery were 94.4% and 100%, respectively (P = 0.2153). Both groups showed significant improvement after 1 year for International Prostate Symptom Score total and quality of life score, Overactive Bladder Symptom Score total score, voided volume, maximum urinary flow rate and post-void residual. [Corrections added on 7 September 2021 after first online publication: the first two P-values have been updated.] CONCLUSIONS: The combined use of sutures and tackers in laparoscopic sacrocolpopexy simplifies the procedure and translates into shorter operation time. Surgical outcomes at 1 year and improvement of lower urinary tract symptoms are similar regardless of the technique., (© 2021 The Japanese Urological Association.)

Background: Surgical treatments for renal cell carcinoma reduces kidney volume to some degree and may derive postsurgical chronic kidney disease. We made a new marker for postoperative renal function using CT volumetry. To determine the impact of various parameters including this marker, we observed pre- and postsurgical renal function of experienced cases., Methods: From 2004 to 2014, we underwent total or partial nephrectomy for 181 patients with renal carcinoma in a single institution. Of the total, 138 cases with presurgical CT volumetry were included in this study. We evaluated parameters for assessments of peri- and postoperative renal function including age, gender, serum creatinine, eGFR, performed surgery, pathology, estimated residual kidney volume and associated disease. Presence or absence of acute kidney injury (AKI) and chronic kidney disease (CKD) were also evaluated before, immediately after and 5 years after surgery., Results: Multiple logistic regression analysis identified AKI, preoperative eGFR and estimated residual kidney volume as significant prognostic factors for the postoperative CKD. Moreover, cases with triple positive of these factors suffer postoperative CKD more significantly than those with one or two positives., Conclusion: Using these predictive factors, we may determine patients with high risk for CKD who require an early intervention of renal protective treatment.

Natural chlorophylls have a D-ring reduced chlorin π-system; however, no naturally occurring photosynthetically active B-ring reduced chlorins have been reported. Here we report a B-ring reduced chlorin, 17,18-didehydro-bacteriochlorophyll (BChl) a, produced by in situ oxidation of B800 bacteriochlorophyll (BChl) a in a light-harvesting protein LH2 from a purple photosynthetic bacterium Phaeospirillum molischianum. The regioselective oxidation of the B-ring of B800 BChl a is rationalized by its molecular orientation in the protein matrix. The formation of 17,18-didehydro-BChl a produced no change in the local structures and circular arrangement of the LH2 protein. The B-ring reduced 17,18-didehydro-BChl a functions as an energy donor in the LH2 protein. The photoactive B-ring reduced Chl isomer in LH2 will be helpful for understanding the photofunction and evolution of photosynthetic cyclic tetrapyrrole pigments.

Background: The aim of this paper was to evaluate the efficacies and safety of transurethral prostate enucleation by bipolar system (TUEB) for the patients with benign prostatic hyperplasia (BPH)., Methods: We prospectively evaluated clinical outcomes of TUEB in 55 patients with BPH from July 2005 to January 2011. Mean ages of the patients were 69.2 years. International Prostate Symptom Score (IPSS), IPSS-quality of life (IPSS-QOL) were assessed before and 12 months after surgery. Serum PSA, maximal flow rate (MFR), and post-void residual (PVR) were also evaluated before and 6 and 12 months after surgery., Results: The median prostate volumes and resection volumes were 64.1 g (interquartile range [IQR]: 48-87) and 34.4 g (25-60.2), respectively. The median operation time was 138.0 min (100.2-169.2). Total IPSS scores and IPSS-QOL were significantly improved (from 24 [17-31] to 5 [2-8] points, and from 6 [5-6] to 2 [1-2] points, both P<0.001). MFR and PVR were significantly improved 6 and 12 months after TUEB (from 6.2 [3.9-8.3] to 15.1 [10.5-20.9], and 14.6 [10.2-20.5] mL/s, P<0.0001, and from 151.5 [81.5-284.7] to 16.5 [0-30.5], and 6.0 [0-41.0] mL, P<0.0001, respectively). Serum PSA also significantly decreased, 6 and 12 months (from 7.5 [4.7-9.8] to 1.1 [0.5-1.5], and 0.6 [0.3-1.9] ng/mL, P<0.0001). Although hemoglobin decreased after operation, no case experienced blood transfusion. Three episodes of urinary tract infections, 14 cases of mild stress urinary incontinence, 2 cases of urinary retention were occurred transiently with recovery within 1 month after surgery., Conclusions: We identified favorable efficacy and safety of TUEB. TUEB appears to be another possibility in the treatment of BPH.

In order to improve the reproductive performance during the summer period, embryo transfer (ET; Japanese black embryo) following artificial insemination (AI; Holstein semen: ETFAI) was conducted in dairy cows in south-western Japan (n=56). The conception rate was improved in cows with ETFAI compared with conventional AI, which served as the control (n=195; 30.4% vs. 13.8%, P<0.01). However, higher fetal loss was observed in ETFAI compared with the controls (38.1% vs. 7.4%, P<0.05). Four cases of twin pregnancy resulted in 2 singletons and a set of twins. There was no difference in the plasma progesterone level on d0 or d7 (d0=AI), but rather lower rectal temperature was observed on d7 or d8 (38.7 degrees C vs. 39.4 degrees C and 38.8 degrees C vs. 39.1 degrees C, P<0.05) in pregnant cows compared with those that were open. ETFAI could improve reproductive performance in dairy cows during the summer period in south-western Japan.