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Introduction: As glomerular filtration rate (GFR) decreases, serum phosphate level increases. Previous reports indicated that serum phosphate level was associated with mortality in patients on dialysis. However, few reports have examined the association using dialysis initiation as the baseline period. Methods: This was a multicenter prospective cohort analysis including 1492 patients. Patients were classified into four quartiles based on the serum phosphate level at dialysis initiation, with Q1 being the lowest and Q4 the highest. All-cause mortality after dialysis initiation was compared using the log-rank test. The propensity score represented the probability of being assigned to group Q1 or Q2-4. All-cause mortality was compared in propensity score-matched patients by using the log-rank test for Kaplan-Meier curves. All-cause mortality of Q1 was compared with that for Q2-4 using multivariate Cox proportional hazard regression analysis. All-cause mortality was also determined among stratified groups with or without use of phosphate binders. Results: Significant differences in cumulative survival rates were observed between the four groups (p < .001). After propensity score-matching, mortality was significantly higher in the Q1 group than the Q2-4 group (p = .046). All-cause mortality was significantly higher in the Q1 group after adjustment for history of CAD (hazard ratio [HR] = 0.76, 95% confidence interval [CI]: 0.58 − 1.00, p = .048). However, there was no significant difference between the two groups after adjustment for estimated GFR. Conclusion: The serum phosphate level at the time of dialysis initiation was associated with all-cause mortality. However, the serum phosphate level was dependent on the renal function. [ABSTRACT FROM AUTHOR]

Background/Aim: High serum alkaline phosphatase (ALP) levels predict mortality independent of bone metabolism parameters and liver function test results in patients on hemodialysis. The relationship between serum ALP at dialysis initiation and mortality during maintenance dialysis is unknown; therefore, we aimed to identify an association. Methods: This multicenter, prospective cohort study analyzed 1,213 patients registered in the Aichi Cohort Study of Prognosis in Patients Newly Initiated into Dialysis from October 2011 to September 2013. Patients were divided into 2 groups based on serum ALP levels. All-cause mortality and incidences of cardiovascular events after dialysis initiation were compared using the log-rank test and multivariate Cox proportional hazard regression analysis. We performed stratified analysis based on parathyroid hormone (PTH) levels. Results: During the follow-up, 109 (18.0%) and 86 (14.1%) patients died in the high ALP group (232 ≥IU/L; High ALP group) and low ALP group (232

Although cytochrome P45017α catalyzes the formation of androgen from both pregnenolone and progesterone, the production of androstenedione from progesterone is a major pathway in the guinea pig, rat, mouse, and hamster. In contrast, human, bovine and sheep P45017α produce dehydroepiandrosterone from pregnenolone. Cytochrome P45017αs from all of these animals have high homology in the amino acid sequence around the 340–370 region. To investigate the substrate preferences for androgen production, we replaced a few amino acids in the 340–370 region of guinea pig P45017α with those found in the other animals. The recombinant P45017αs were expressed in E. coli DH5α, purified by column chromatography and incorporated into liposome membranes. The (His)4 tag in the recombinant P45017αs had little effect on the interaction with NADPH–P450 reductase in the membranes. The recombinant P45017αs with a single-position mutation of F344I, H349R or M352L and with double-position mutations of F344I and H349R and triple-position mutations showed decreases in the production of 17α-hydroxypregnenolone, androstenedione and dehydroepiandrosterone. The activity for 17α-hydroxyprogeterone production was increased significantly by the F344I mutation. The addition of cytochrome b5 did not have much of an effect on the 17α-hydroxylation but had a significant effect on androgen production in both the nonmutated and mutated P45017αs. [Copyright &y& Elsevier]

Background/aim: The frequency rate of injection site reactions (ISR) due to fosaprepitant meglumine (Fos APR) has been shown to vary depending on the types of combined anticancer drug. This study aimed to elucidate the impact of Fos APR on ISR in patients receiving paclitaxel and carboplatin, with and without bevacizumab therapy (TC±Bev)., Patients and Methods: This study focused on patients with gynecologic cancer (n=93) who received TC±Bev administration at Fujita Health University Hospital from March 2016 to February 2020, and monitored up to six cycles. The patients were randomly assigned to the Fos APR group (n=47) and the Aprepitant (APR) group (n=46). Using Visual Infusion Phlebitis (VIP) scores, ISR was evaluated by comparing the VIP scores of all cycles using a linear mixed model. The risk factors that contribute to the occurrence of vascular pain throughout all cycles were also examined., Results: The VIP scores of all cycles showed a near significant intergroup difference (p=0.071). Factors that affected the development of vascular pain included Fos APR and age (p=0.027 and 0.049, respectively). Regarding age, patients aged <65 years had a higher risk. Four patients underwent a switch from the originally assigned neurokinin-1 receptor antagonist; in all of these cases, Fos APR was changed to APR for vascular pain., Conclusion: Fos APR may increase the risk for ISR associated with TC±Bev therapy for gynecological cancer., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Introduction: Human epidermal growth factor receptor (HER)-2 overexpression or gene amplification is more common in high-grade or type 2 endometrial carcinomas. We assessed the discordance of HER-2 expression between primary and metastatic or recurrent endometrial carcinomas., Materials and Methods: Thirty-six primary, along with 14 metastatic and five recurrent tumors (matched to primaries), pathologically confirmed as high-grade or type 2 endometrial carcinomas, were submitted for immunohistochemistry (IHC) for HER-2. Fluorescence in situ hybridization was performed when the tumors showed HER-2 overexpression (≥2+ IHC score). The results of the IHC and fluorescence in situ hybridization assays were compared between the primary and metastatic or recurrent tumors. The relationships between HER-2 expression and clinicopathological factors or prognosis were investigated., Results: HER-2 overexpression and HER-2 amplification (a ratio of HER-2 copies to chromosome 17 [CEP17] copies ≥2.2) were detected in 33.3% (twelve of 36 patients) and 5.6% (two of 36 patients) of primary tumors, respectively. HER-2 overexpression was not associated with clinicopathological factors or prognosis. In 19 tumor specimens obtained from metastatic or recurrent tumors, HER-2 overexpression and HER-2 amplification were detected in 57.9% (eleven patients) and 15.8% (three patients), respectively. HER-2 overexpression tended to predict a worse prognosis., Conclusion: HER-2 expression in metastatic or recurrent tumors was more frequent than in matched primary high-grade or type 2 endometrial carcinomas. Trastuzumab in combination with cytotoxic chemotherapy may represent an alternative therapeutic option for these tumors.

Forkhead transcription factors are characterized by a winged helix DNA binding domain, and the members of this family are classified into 20 subclasses by phylogenetic analyses. Fkhl18 is structurally unique, and is classified into FoxS subfamily. We found Fkhl18 expression in periendothelial cells of the developing mouse fetal testis. In an attempt to clarify its function, we generated mice with Fkhl18 gene disruption. Although KO mice developed normally and were fertile in both sexes, we frequently noticed unusual blood accumulation in the fetal testis. Electron microscopic analysis demonstrated frequent gaps, measuring 100-400 nm, in endothelial cells of blood vessels. These gaps probably represented ectopic apoptosis of testicular periendothelial cells, identified by caspase-3 expression, in KO fetuses. No apoptosis of endothelial cells was noted. Fkhl18 suppressed the transcriptional activity of FoxO3a and FoxO4. Considering that Fas ligand gene expression is activated by Foxs, the elevated activity of Foxs in the absence of Fkhl18 probably explains the marked apoptosis of periendothelial cells in Fkhl18 KO mice.

Mice with disrupted mammalian PcG (Polycomb group) genes commonly show skeletal transformation of anterior-posterior identities. Disruption of the murine M33 gene, a PcG member, displayed posterior transformation of the vertebral columns and sternal ribs. In addition, failure of T-cell expansion and hypoplasia and sex-reversal of the gonads, have been observed. In the present study, we identified defects in the splenic and adrenal formation of M33-knock-out (KO) mice on a C57BL/6 genetic background. The spleen in these animals was smaller than in the wild-type mice and was spotted red because of nonuniform distribution of blood cells. Histologic examination revealed disorganization of the vascular endothelium and its surrounding structures, and immunohistochemistry demonstrated disturbances in vascular formation and colonization of immature hematopoietic cells. These splenic phenotypes observed in the M33-KO mice were quite similar to those seen in Ad4BP/SF1 (Nr5a1) knock-outs. Moreover, the adrenal glands of M33-KO and Ad4BP/SF1 heterozygous KO mice were smaller than those of the wild-type mice. Western blot, immunohistochemistry, and reverse transcriptase-polymerase chain reaction (RT-PCR) analyses of the M33 knock-outs all indicated significantly low expression of adrenal 4 binding protein/steroidogenic factor-1 (Ad4BP/SF-1), indicating that M33 is an essential upstream regulator of Ad4BP/SF1. In agreement with these observations, chromatin immunoprecipitation assays with adrenocortical Y-1 cells revealed direct binding of the M33-containing PcG to the Ad4BP/SF1 gene locus.