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Abstract Background We previously conducted a retrospective Japanese cohort study of patients who underwent radical prostatectomy (RP) between January 2010 and December 2020 in Ehime Prefecture. This study revealed an increase in the number of RP, but other treatment trends remained unclear. In the current study, we examined prostate cancer treatment in Ehime Prefecture using the hospital-based cancer registry of all designated cancer care hospitals and community cancer care hospitals belonging to the Council of Ehime Cancer Care Hospitals. Methods Trends of prostate cancer were compared by year according to stage and treatment using data from the hospital-based cancer registry between 2011 and 2020. Results The number of patients with stage 1 disease increased over time, but the proportion of patients with stage 1 disease among all patients decreased from 65.2% in 2012 to 56.9% in 2020. The number of patients with stage 2 disease also increased, but the proportion of such patients among all patients remained constant. Meanwhile, the proportions of patients with stage 3 or 4 disease increased significantly over time, while that of patients undergoing RP increased from 29.2% in 2011 to 45.7% in 2020 (P

This study classifies fetal inflammatory response syndrome (FIRS) based on the presence or absence of maternal-fetal inflammation in the placenta and clarifies the association of FIRS with neonatal morbidities. Women (330) who delivered at gestational ages of 22w0d-33w6d were enrolled and grouped into four based on FIRS and maternal/fetal inflammatory response (MIR/FIR) statuses: Group A: without FIRS and MIR/FIR (reference group); Group B: MIR/FIR alone; Group C: FIRS and MIR/FIR; and Group D: FIRS without MIR/FIR. The associations between bronchopulmonary dysplasia (BPD), adverse neonatal outcomes, extremely low gestational age and Groups B, C, and D were investigated after adjustment for potential confounders. Among patients with FIRS, 29% were in Group D. The risk of BPD was increased in Groups C (adjusted odds ratio (aOR): 3.36; 95% confidence interval (CI): 1.14–9.89) and D (aOR: 4.17; 95% CI: 1.03–16.9), as was the risk of adverse neonatal outcomes (Group C: aOR: 7.17; 95% CI: 2.56–20.1; Group D: aOR: 6.84; 95% CI: 1.85–25.2). The risk of extremely low gestational age was increased in Group D (aOR: 3.85; 95% CI: 1.56–9.52). Therefore, FIRS without MIR/FIR is not rare and may be associated with neonatal morbidities more than FIRS and MIR/FIR.

It has been reported that supply of nitrate to culture solution rapidly and reversibly inhibits nodule growth and nitrogen fixation activity of soybean. In this study, the effects of ammonium, urea, or glutamine on nodule growth and nitrogen fixation activity are compared with that for nitrate. Soybean plants were cultivated with a nitrogen-free nutrient solution, then 1 mM-N of nitrate, ammonium, glutamine, or urea were supplied from 12 DAP until 17 DAP. Repression of nodule growth and nitrogen fixation activity at 17 DAP were observed by ammonium, urea, and glutamine like nitrate, although the inhibitory effects were milder than nitrate. The removal of nitrogen from the culture solutions after nitrogen treatments resulted in a recovery of the nodule growth. It was found that the glutamine treatment followed by N-free cultivation gave highest nitrogen fixation activity about two times of the control. Tracer experiments with 15N and 13C were performed to evaluate the translocation of N and C to the different tissues. Culture solutions containing a 15N-labeled nitrogen source were supplied from 21 DAP, and the whole shoots were exposed to 13CO2 for 60 min on 23 DAP, and plants were harvested on 24 DAP. The percentage distribution of 15N in nodules was highest for ammonium (1.4%) followed by glutamine (0.78%), urea (0.32%) and nitrate (0.25%). The percentage distribution of 13C in the nodules was highest for the control (11.5%) followed by urea (5.8%), glutamine (2.6%), ammonium (2.3%), and nitrate (2.3%). The inhibitory effects of nitrogen compounds appeared to be related to a decrease in photoassimilate partitioning in the nodules, rather than 15N transport into the nodules. The free amino acid concentrations after nitrogen treatments were increased in the nodules and leaves by nitrate, in the roots by ammonium, in the stems by urea, and the roots, stems, and leaves by glutamine treatment. The concentrations of asparagine, aspartate, and glutamine were increased after nitrogen treatments. By the long-term supply of nitrogen for 2-weeks, nitrate significantly increased the lateral roots and leaf growth. The long-term supply of urea and glutamine also promoted the lateral roots and leaf growth, but ammonium suppressed them.

Objective The mortality of patients with locally advanced triple-negative breast cancer (TNBC) is high, and pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) is associated with improved prognosis. This retrospective study was designed and powered to investigate the ability of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) to predict pathological response to NAC and prognosis after NAC.Methods The data of 32 consecutive women with clinical stage II or III TNBC from January 2006 to December 2013 in our institution who underwent FDG-PET/CT at baseline and after NAC were retrospectively analyzed. The maximum standardized uptake value (SUVmax) in the primary tumor at each examination and the change in SUVmax (ΔSUVmax) between the two scans were measured. Correlations between PET parameters and pathological response, and correlations between PET parameters and disease-free survival (DFS) were examined.Results At the completion of NAC, surgery showed pCR in 7 patients, while 25 had residual tumor, so-called non-pCR. Median follow-up was 39.0 months. Of the non-pCR patients, 9 relapsed at 3 years. Of all assessed clinical, biological, and PET parameters, N-stage, clinical stage, and ΔSUVmax were predictors of pathological response (p=0.0288, 0.0068, 0.0068; Fischer’s exact test). The cut-off value of ΔSUVmax to differentiate pCR evaluated by the receiver operating characteristic (ROC) curve analysis was 81.3%. Three-year disease-free survival (DFS) was lower in patients with non-pCR than in patients with pCR (p=0.328, log-rank test). The cut-off value of ΔSUVmax to differentiate 3-year DFS evaluated by the ROC analysis was 15.9%. In all cases, 3-year DFS was lower in patients with ΔSUVmax

Zebrafish are used widely in biomedical, toxicological, and developmental research, but information on their xenobiotic metabolism is limited. Here, we characterized the expression of 14 xenobiotic cytochrome P450 (CYP) subtypes in whole embryos and larvae of zebrafish (4 to 144 h post-fertilization (hpf)) and the metabolic activities of several representative human CYP substrates. The 14 CYPs showed various changes in expression patterns during development. Many CYP transcripts abruptly increased at about 96 hpf, when the hepatic outgrowth progresses; however, the expression of some cyp1s (1b1, 1c1, 1c2, 1d1) and cyp2r1 peaked at 48 or 72 hpf, before full liver development. Whole-mount in situ hybridization revealed cyp2y3, 2r1, and 3a65 transcripts in larvae at 55 hpf after exposure to rifampicin, phenobarbital, or 2,3,7,8-tetrachlorodibenzo-p-dioxin from 30 hpf onward. Marked conversions of diclofenac to 4′-hydroxydiclofenac and 5-hydroxydiclofenac, and of caffeine to 1,7-dimethylxanthine, were detected as early as 24 or 50 hpf. The rate of metabolism to 4’-hydroxydiclofenac was more marked at 48 and 72 hpf than at 120 hpf, after the liver had become almost fully developed. These findings reveal the expression of various CYPs involved in chemical metabolism in developing zebrafish, even before full liver development.

This paper reports the synthesis of D-A polymers containing 1,2-dithienylethene (DTE) units via palladium-catalyzed direct arylation polymerization (DArP). The reaction of dibromoisoindigo (1-Br) and DTE (2-H), in the presence of Pd2(dba)3·CHCl3 (0.5 mol%), P(2-MeOC6H4)3 (L1) (2 mol%), pivalic acid (1 equiv) as catalyst precursors, and Cs2CO3 (3 equiv) as a base affords poly(1-alt-2) with a high molecular weight (Mn up to 44,900). Although, it has been known that monomers, with plural C–H bonds, tend to form insoluble materials via direct arylation at undesirable C–H positions; the reaction of 1-Br and 2-H cleanly proceeds without insolubilization. The resulting polymer has a well-controlled structure and exhibits good charge transfer characteristics in an organic field-effect transistor (OFET), compared to the polymer produced by Migita–Kosugi–Stille cross-coupling polymerization. The DArP product displays an ideal linear relationship in the current–voltage curve, whereas the Migita–Kosugi–Stille product shows a VG-dependent change in the charge mobility.

Objective: To clarify the frequency of deficient mismatch repair (dMMR) in Japanese ovarian cancer patients, we examined microsatellite instability (MSI) status and immunohistochemistry (IHC) subtypes, including endometrioid carcinoma (EMC), clear cell carcinoma (CCC), or a mixture of both (Mix). Methods: We registered 390 patients who were diagnosed with EMC/CCC/Mix between 2006 and 2015 and treated at seven participating facilities. For 339 patients confirmed eligible by the Central Pathological Review Board, MSI, IHC, and MutL homolog 1 methylation analyses were conducted. The tissues of patients with Lynch syndrome (LS)-related cancer histories, such as colorectal and endometrial cancer, were also investigated. Results: MSI-high (MSI-H) status was observed in 2/217 CCC (0.9%), 10/115 EMC (8.7%), and 1/4 Mix (25%). Additionally, loss of MMR protein expression (LoE-MMR) was observed in 5/219 (2.3%), 16/115 (14.0%), and 1/4 (25%) patients with CCC, EMC, and Mix, respectively. Both MSI-H and LoE-MMR were found significantly more often in EMC (p<0.001). The median (range) ages of patients with MMR expression and LoE-MMR were 54 (30-90) and 46 (22-76) (p=0.002), respectively. In the multivariate analysis, advanced stage and histological type were identified as prognostic factors. Conclusion: The dMMR rate for EMC/CCC was similar to that reported in Western countries. In Japan, it is assumed that the dMMR frequency is higher because of the increased proportion of CCC. [ABSTRACT FROM AUTHOR]

Objective(s): The mortality of patients with locally advanced triple-negative breast cancer (TNBC) is high, and pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) is associated with improved prognosis. This retrospective study was designed and powered to investigate the ability of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) to predict pathological response to NAC and prognosis after NAC. Methods: The data of 32 consecutive women with clinical stage II or III TNBC from January 2006 to December 2013 in our institution who underwent FDG-PET/CT at baseline and after NAC were retrospectively analyzed. The maximum standardized uptake value (SUVmax) in the primary tumor at each examination and the change in SUVmax (ΔSUVmax) between the two scans were measured. Correlations between PET parameters and pathological response, and correlations between PET parameters and disease-free survival (DFS) were examined. Results: At the completion of NAC, surgery showed pCR in 7 patients, while 25 had residual tumor, so-called non-pCR. Median follow-up was 39.0 months. Of the non-pCR patients, 9 relapsed at 3 years. Of all assessed clinical, biological, and PET parameters, N-stage, clinical stage, and ΔSUVmax were predictors of pathological response (p value of 0.0288, 0.0068, 0.0068 respectively; Fischer's exact test). The cut-off value of ΔSUVmax to differentiate pCR evaluated by the receiver operating characteristic (ROC) curve analysis was 81.3%. Three-year disease-free survival (DFS) was lower in patients with nonpCR than in patients with pCR (p=0.328, log-rank test). The cut-off value of ΔSUVmax to differentiate 3-year DFS evaluated by the ROC analysis was 15.9%. In all cases, 3-year DFS was lower in patients with ΔSUVmax <15.9% than in patients with ΔSUVmax =15.9% (p=0.0078, log-rank test). In non-pCR patients, 3-year DFS was lower in patients with ΔSUVmax <15.9% than in patients with ΔSUVmax =15.9% (p=0.0238, log-rank test). Conclusion: FDG-PET/CT at baseline and after NAC could predict pathological response to NAC before surgery and the clinical outcome after surgery in locally advanced TNBC patients. [ABSTRACT FROM AUTHOR]

Aims Personalised breast cancer therapy requires pathological characterisation of tumours. The proliferative index, based on Ki67, is pivotal, but a standard method has not been established. Here we look for an easy and practical way to evaluate Ki67. Methods Immunohistochemical staining of estrogen receptors, progesterone receptors, HER2 and Ki67 (MIB-1) was performed on resected specimens from 406 primary invasive ductal carcinomas. Ki67 labelling index (LI) from manual counting was compared with visual assessment using a 5-grade scale (Eye-5). Next, 10 pathologists evaluated 100 samples with marked hot spots by using Eye-5. Another 100 samples without marking were also assessed by eight pathologists. One year later, two pathologists reviewed 222 cases with Eye-5. Prognosis was analysed among estrogen receptorpositive cases with postoperative endocrine therapy. Results Eye-5 showed good correlation to LI. All 136 cases of score 4-5 had LI >20% and all 56 cases of score 1 had LI<20%, which means that manual counting was not necessary for about half of the cases. Interobserver and intraobserver variability was low even when a hot spot was not fixed. Eye-5 also correlated with histological grade and lymph node metastasis. Combining Eye-5 and histological grade created a new algorism to predict LI, which allows 80% of all cases (74% of luminal cases) without manual counting. Cases of Eye-5 score 1-2 had significantly better survival than score 3-5. Conclusions Visual assessment of Ki67 by a 5-grade scale (Eye-5) is fast, easy, and reliable with acceptably low interobserver and intraobserver variability. Eye-5 can replace LI in many luminal tumours, and is a strong candidate as a standard method of evaluating Ki67. [ABSTRACT FROM AUTHOR]

The article discusses a study which aimed to identify risk factors for lung cancer recurrence after cancer resection using the survival tree method. The results show that the T factor, the N factor, and lymphatic (ly) and blood (v) vessel invasion were related to the risk of recurrence. It cooncluded that by combining the T, N, v, and ly factors allowed the precise identification of a group with a high risk of recurrence following resection.

Increasing use of zebrafish in biomedical, toxicological and developmental studies requires explicit knowledge of cytochrome P450 (CYP), given the central role of CYP in oxidative biotransformation of xenobiotics and many regulatory molecules. A full complement of CYP genes in zebrafish and their transcript expression during early development have already been examined. Here we established a comprehensive picture of CYP gene expression in the adult zebrafish liver using a RNAseq technique. Transcriptional profiling of a full complement of CYP genes revealed that CYP2AD2, CYP3A65, CYP1A, CYP2P9 and CYP2Y3 are major CYP genes expressed in the adult zebrafish liver in both sexes. Quantitative real-time RT-PCR analysis for selected CYP genes further supported our RNAseq data. There were significant sex differences in the transcript levels for CYP1A, CYP1B1, CYP1D1 and CYP2N13, with males having higher expression levels than those in females in all cases. A similar feature of gender-specific expression was observed for CYP2AD2 and CYP2P9, suggesting sex-specific regulation of constitutive expression of some CYP genes in the adult zebrafish liver. The present study revealed several "orphan" CYP genes as dominant isozymes at transcript levels in the adult zebrafish liver, implying crucial roles of these CYP genes in liver physiology and drug metabolism. The current results establish a foundation for studies with zebrafish in drug discovery and toxicology. [ABSTRACT FROM AUTHOR]