LsMybW-encoding R2R3-MYB transcription factor is responsible for a shift from black to white in lettuce seed.

KEY MESSAGE: We identified LsMybW as the allele responsible for the shift in color from black to white seeds in wild ancestors of lettuce to modern cultivars. Successfully selected white seeds are a key agronomic trait for lettuce cultivation and breeding; however, the mechanism underlying the shift from black-in its wild ancestor-to white seeds remains uncertain. We aimed to identify the gene/s responsible for white seed trait in lettuce. White seeds accumulated less proanthocyanidins than black seeds, similar to the phenotype observed in Arabidopsis TT2 mutants. Genetic mapping of a candidate gene was performed with double-digest RAD sequencing using an F2 population derived from a cross between "ShinanoPower" (white) and "Escort" (black). The white seed trait was controlled by a single recessive locus (48.055-50.197 Mbp) in linkage group 7. Using five PCR-based markers and numerous cultivars, eight candidate genes were mapped in the locus. Only the LG7_v8_49.251Mbp_HinfI marker, employing a single-nucleotide mutation in the stop codon of Lsat_1_v5_gn_7_35020.1, was completely linked to seed color phenotype. In addition, the coding region sequences for other candidate genes were identical in the resequence analysis of "ShinanoPower" and "Escort." Therefore, we proposed Lsat_1_v5_gn_7_35020.1 as the candidate gene and designated it as LsMybW (Lactuca sativa Myb White seeds), an ortholog encoding the R2R3-MYB transcription factor in Arabidopsis. When we validated the role of LsMybW through genome editing, LsMybW knockout mutants harboring an early termination codon showed a change in seed color from black to white. Therefore, LsMybW was the allele responsible for the shift in seed color. The development of a robust marker for marker-assisted selection and identification of the gene responsible for white seeds have implications for future breeding technology and physiological analysis.

Computed Tomography Renal Volumetry Better Predicts Postoperative Donor Renal Function in Live Kidney Donor Transplantation than Renal Scintigraphy: A Comparative Study.

INTRODUCTION AND OBJECTIVES: Both computed tomography (CT) and renal scintigraphy (RS) have been used to assess vascular anatomy, renal status, and split renal function (SRF). In this study, we used a recently developed software that facilitates renal volumetric evaluations to compare RS and automated CT volumetry for assessing residual renal function and, thus, estimating postoperative renal function after donor nephrectomy. METHODS: Fifty-one cases of donor nephrectomy were analyzed. Residual renal function was estimated based on RS and CT volumetry. The correlation between the postoperative estimated glomerular filtration rate (eGFR) and expected SRF, measured using RS and three types of CT volumetry data (ellipsoid, thin-slice, and 5-mm slice data), was determined. RESULTS: The correlation coefficient between actual eGFR and expected SRF was significantly associated at each time point and modality (p < 0.0001). At any time point, the difference in correlation coefficient between RS and 5-mm volumetry was significant (p value: 0.003-0.018), whereas the differences in correlation coefficients between RS and the triaxial volume calculation, and the triaxial volume calculation and 5-mm volumetry, were generally statistically insignificant. CONCLUSIONS: Expected SRF was estimated more accurately by CT volumetric calculations (especially 5-mm slice-based volumetry) than RS.

Simplified approach to the medial internal iliac region using a uretero-hypogastric nerve fascia development procedure for extended pelvic lymph node dissection during robot-assisted radical prostatectomy for high-risk prostate cancer.

INTRODUCTION: Although several clinical guidelines for prostate cancer (PC) recommend extended pelvic lymph node dissection (ePLND) during radical prostatectomy for high-risk cases, there are several issues to consider, including certain technical aspects. A simplified approach to the medial internal iliac region and paravesical arteries has not been established. The uretero-hypogastric nerve fascia (UHF) envelopes the ureter, hypogastric nerve, and pelvic autonomic nerves. To preserve the UHF, it is possible to approach the medial side of the internal iliac vessels without injuring any important tissue. We analyzed technical feasibility and lymph node (LN) yields. PATIENTS AND METHODS: After obtaining institutional review board approval, 265 high-risk PC patients with ePLND were identified. A da Vinci S or Xi robotic surgical system (Intuitive Surgical, Sunnyvale, CA, USA) was used. We divided the patients into conventional (non-UHF) method and modified (UHF) groups. The numbers of LNs removed, procedure-related complications, and surgical outcomes were analyzed. RESULTS: The median number of LNs removed was 19.0 in the non-UHF group and 22.0 in the UHF group (p = 0.004). Significantly more LNs were removed from the internal iliac region in the UHF group (p = 0.042). There was no difference in overall operative, console, or LN dissection time, or the severe complication rate (Clavien-Dindo grade ≥ III), between the non-UHF and UHF groups. CONCLUSIONS: Our simplified approach using the UHF development technique is technically feasible, has no major complications, and allows for the removal of significantly more LNs compared with the conventional method.

[A Case of Multiple Renal Carcinomas with Three Different Subtypes].

We report a case of dialysis kidney with multiple renal carcinomas in three locations. A 74-year-old man who had a 20-year history of dialysis, was admitted to our hospital complaining of sudden right lateral area pain. Computed tomography (CT) scan revealed hemorrhage from the right dialyzed renal subcapsule. He underwent immediate transcatheter arterial embolization (TAE), but after 6 days the CT scan showed new active bleeding. A second TAE was performed, but, the CT scan several days later showed hemorrhage from the same site. So we decided to perform a right radical nephrectomy. Pathological results revealed three different renal carcinomas at sites different from the bleeding site. The presence of triple carcinomas in the same organ of the kidney is quite rare. Because of the high incidence of renal carcinoma associated with polycystic kidney disease in long-term hemodialysis patients and the possibility of multiple carcinomas as in this case, radical nephrectomy is recommended even in the case of spontaneous rupture.

Archetypal Roles of an Abscisic Acid Receptor in Drought and Sugar Responses in Liverworts.

Abscisic acid (ABA) controls seed dormancy and stomatal closure through binding to the intracellular receptor Pyrabactin resistance1 (Pyr1)/Pyr1-like/regulatory components of ABA receptors (PYR/PYL/RCAR) in angiosperms. Genes encoding PYR/PYL/RCAR are thought to have arisen in the ancestor of embryophytes, but the roles of the genes in nonvascular plants have not been determined. In the liverwort Marchantia polymorpha, ABA reduces growth and enhances desiccation tolerance through increasing accumulation of intracellular sugars and various transcripts such as those of Late Embryogenesis Abundant (LEA)-like genes. In this study, we analyzed a gene designated MpPYL1, which is closely related to PYR/PYL/RCAR of angiosperms, in transgenic liverworts. Transgenic lines overexpressing MpPYL1-GFP showed ABA-hypersensitive growth with enhanced desiccation tolerance, whereas Mppyl1 generated by CRISPR-Cas9-mediated genome editing showed ABA-insensitive growth with reduced desiccation tolerance. Transcriptome analysis indicated that MpPYL1 is a major regulator of abiotic stress-associated genes, including all 35 ABA-induced LEA-like genes. Furthermore, these transgenic plants showed altered responses to extracellular Suc, suggesting that ABA and PYR/PYL/RCAR function in sugar responses. The results presented here reveal an important role of PYR/PYL/RCAR in the ABA response, which was likely acquired in the common ancestor of land plants. The results also indicate the archetypal role of ABA and its receptor in sugar response and accumulation processes for vegetative desiccation tolerance in bryophytes.

Decoding ABA and osmostress signalling in plants from an evolutionary point of view.

The plant hormone abscisic acid (ABA) is fundamental for land plant adaptation to water-limited conditions. Osmostress, such as drought, induces ABA accumulation in angiosperms, triggering physiological responses such as stomata closure. The core components of angiosperm ABA signalling are soluble ABA receptors, group A protein phosphatase type 2C and SNF1-related protein kinase2 (SnRK2). ABA also has various functions in non-angiosperms, however, suggesting that its role in adaptation to land may not have been angiosperm-specific. Indeed, among land plants, the core ABA signalling components are evolutionarily conserved, implying their presence in a common ancestor. Results of ongoing functional genomics studies of ABA signalling components in bryophytes and algae have expanded our understanding of the evolutionary role of ABA signalling, with genome sequencing uncovering the ABA core module even in algae. In this review, we describe recent discoveries involving the ABA core module in non-angiosperms, tracing the footprints of how ABA evolved as a phytohormone. We also cover the latest findings on Raf-like kinases as upstream regulators of the core ABA module component SnRK2. Finally, we discuss the origin of ABA signalling from an evolutionary perspective.

One-surgeon basketing technique for stone extraction during flexible ureteroscopy for urolithiasis: A comparison between novice and expert surgeons.

OBJECTIVE: To determine the safety and efficacy of the one-surgeon basketing technique for stone extraction during flexible ureteroscopy when carried out by novice surgeons under instructor guidance. METHODS: We retrospectively compared perioperative results, complications and the "stone-free" rate (defined as ≤2 mm fragments on kidney-ureter-bladder imaging 1 month after flexible ureteroscopy) between experienced (group A, n = 50) and novice (group B, n = 50) surgeons using the one-surgeon basketing technique. RESULTS: Baseline patients' characteristics were similar between the two groups. There were no significant differences between groups A and B in operative time (mean 76 min vs 85 min, P = 0.46), stone-free rate (98% vs 92%, P = 0.36), postoperative fever events (4% vs 4%, P = 1.00) and postoperative hospital stay (24 h vs 24 h, P = 1.00). Clavien-Dindo grade IIIa complications (ureter injury) were only observed in two cases (4%) in group B. CONCLUSIONS: The one-surgeon basketing technique for the extraction of stone fragments during flexible ureteroscopy might be safely and effectively carried out by surgeons with no prior experience under proper guidance.

[A Case of a Congenital Right External Iliac Vein Defect Found after Robot-Assisted Radical Prostatectomy].

Congenital external iliac vein defects are extremely rare. A 56-year-old man underwent robotic prostatectomy (RARP) without pelvic lymph node dissection (PLND) for localized low-risk prostate cancer. Intraoperative findings revealed a markedly dilated vein on the dorsal side of the pubic bone,which was difficult to preserve and was therefore clipped. Sudden swelling and pain appeared in the right leg on day 2 after successful RARP. A contrast-enhanced computed tomography (CT) scan showed a deep vein thrombus (DVT) and lack of a right external iliac vein. Immediate heparinization improved the symptoms, and no other postoperative complications occurred. In the retrospective review,a large dilated vein lying transversely on the prostate surface was observed with a robotic scope,but no manipulation of the pelvic vessels was performed because PLND was not performed. Therefore,the dilated vein was not recognized as a shunt from the right femoral vein to the left external iliac vein. A preoperative staging CT scan,which faintly revealed the right external iliac vein,could be useful to identify this extremely rare deformity in advance of surgery. Although preoperative imaging examinations are often difficult to diagnose preoperatively,as in this case,we consider it important to use appropriate approaches and treatment when dealing with symptoms that arise during pelvic surgery in patients with many anatomical variations.

Plant Raf-like kinase integrates abscisic acid and hyperosmotic stress signaling upstream of SNF1-related protein kinase2.

Plant response to drought and hyperosmosis is mediated by the phytohormone abscisic acid (ABA), a sesquiterpene compound widely distributed in various embryophyte groups. Exogenous ABA as well as hyperosmosis activates the sucrose nonfermenting 1 (SNF1)-related protein kinase2 (SnRK2), which plays a central role in cellular responses against drought and dehydration, although the details of the activation mechanism are not understood. Analysis of a mutant of the moss Physcomitrella patens with reduced ABA sensitivity and reduced hyperosmosis tolerance revealed that a protein kinase designated "ARK" (for "ABA and abiotic stress-responsive Raf-like kinase") plays an essential role in the activation of SnRK2. ARK encoded by a single gene in P. patens belongs to the family of group B3 Raf-like MAP kinase kinase kinases (B3-MAPKKKs) mediating ethylene, disease resistance, and salt and sugar responses in angiosperms. Our findings indicate that ARK, as a novel regulatory component integrating ABA and hyperosmosis signals, represents the ancestral B3-MAPKKKs, which multiplied, diversified, and came to have specific functions in angiosperms.

Oxygen delivery using neonatal self-inflating bags without reservoirs.

BACKGROUND: Guidelines recommend avoiding excessive oxygen during neonatal resuscitation. Recent studies have suggested that oxygen titration can be achieved using a self-inflating bag, but data on the effectiveness of resuscitators used in neonatal ventilation are scarce, The aim of this study was therefore to determine the amount of oxygen delivered using several brands of neonatal self-inflating resuscitation bags without reservoirs under different conditions with regard to oxygen flow rate, ventilation rate (VR), peak inspiratory pressure (PIP) range, and test lung compliance. METHODS: Oxygen concentration was measured under a variety of conditions. Combinations of oxygen flow rate (10, 5.0, 3.0 and 1.0 L/min), VR (40, 60 inflations/min), PIP range (20-25 cmH2 O, 35-40 cmH2 O), and test lung compliance (0.6, 1.0, 3.0, and 5.0 mL/cmH2 O) were examined using six kinds of self-inflating bag. RESULTS: Delivered oxygen concentration varied widely (30.1-96.7%) and had a significant positive correlation with gas flow rate in all of the bags. Delivered oxygen concentration was also negatively correlated with PIP in all of the bags and with VR in some of them. Test lung compliance did not affect delivered oxygen concentration. CONCLUSION: The use of neonatal resuscitation self-inflating bags without reservoirs resulted in different delivered oxygen concentrations depending on gas flow rate, VR, PIP, and manufacturer, but not on lung compliance. This suggests that targeted oxygen concentrations could be delivered, even in lungs with decreased compliance, during resuscitation.

Abscisic acid-induced gene expression in the liverwort Marchantia polymorpha is mediated by evolutionarily conserved promoter elements.

Abscisic acid (ABA) is a phytohormone widely distributed among members of the land plant lineage (Embryophyta), regulating dormancy, stomata closure and tolerance to environmental stresses. In angiosperms (Magnoliophyta), ABA-induced gene expression is mediated by promoter elements such as the G-box-like ACGT-core motifs recognized by bZIP transcription factors. In contrast, the mode of regulation by ABA of gene expression in liverworts (Marchantiophyta), representing one of the earliest diverging land plant groups, has not been elucidated. In this study, we used promoters of the liverwort Marchantia polymorpha dehydrin and the wheat Em genes fused to the ß-glucuronidase (GUS) reporter gene to investigate ABA-induced gene expression in liverworts. Transient assays of cultured cells of Marchantia indicated that ACGT-core motifs proximal to the transcription initiation site play a role in the ABA-induced gene expression. The RY sequence recognized by B3 transcriptional regulators was also shown to be responsible for the ABA-induced gene expression. In transgenic Marchantia plants, ABA treatment elicited an increase in GUS expression in young gemmalings, which was abolished by simultaneous disruption of the ACGT-core and RY elements. ABA-induced GUS expression was less obvious in mature thalli than in young gemmalings, associated with reductions in sensitivity to exogenous ABA during gametophyte growth. In contrast, lunularic acid, which had been suggested to function as an ABA-like substance, had no effect on GUS expression. The results demonstrate the presence of ABA-specific response mechanisms mediated by conserved cis-regulatory elements in liverworts, implying that the mechanisms had been acquired in the common ancestors of embryophytes.

Analysis of grain elements and identification of best genotypes for Fe and P in Afghan wheat landraces.

This study was carried out with the aim of developing the methodology to determine elemental composition in wheat and identify the best germplasm for further research. Orphan and genetically diverse Afghan wheat landraces were chosen and EDXRF was used to measure the content of some of the elements to establish elemental composition in grains of 266 landraces using 10 reference lines. Four elements, K, Mg, P, and Fe, were measured by standardizing sample preparation. The results of hierarchical cluster analysis using elemental composition data sets indicated that the Fe content has an opposite pattern to the other elements, especially that of K. By systematic analysis the best wheat germplasms for P content and Fe content were identified. In order to compare the sensitivity of EDXRF, the ICP method was also used and the similar results obtained confirmed the EDXRF methodology. The sampling method for measurement using EDXRF was optimized resulting in high-throughput profiling of elemental composition in wheat grains at low cost. Using this method, we have characterized the Afghan wheat landraces and isolated the best genotypes that have high-elemental content and have the potential to be used in crop improvement.

Characterization of AtSTOP1 orthologous genes in tobacco and other plant species.

Aluminum (Al) and proton (H⁺) tolerances are essential traits for plants to adapt to acid soil environments. In Arabidopsis (Arabidopsis thaliana), these tolerances are mediated by a zinc-finger transcription factor, SENSITIVE TO PROTON RHIZOTOXICITY1 (AtSTOP1), which regulates the transcription of multiple genes critical for tolerance to both stressors. Here, the functions of orthologous proteins (STOP1-like proteins) in other plant species were characterized by reverse genetics analyses and in planta complementation assays. RNA interference of a gene for NtSTOP1 repressed Al and H⁺ tolerances of tobacco (Nicotiana tabacum) roots. Tobacco roots released citrate in response to Al, concomitant with the up-regulated transcription of an ortholog of an Al tolerance gene encoding a citrate-transporting multidrug and toxic compound extrusion protein. The RNA interference repression of NtSTOP1 blocked this process and also repressed the transcription of another orthologous gene for Al tolerance, ALUMINUM SENSITIVE3, which encodes a prokaryote-type transporter. These results demonstrated that NtSTOP1 regulates Al tolerance in tobacco through the transcriptional regulation of these genes. The in planta complementation assays revealed that other plant species, including woody plants, a legume, and a moss (Physcomitrella patens), possess functional STOP1-like proteins that can activate several H⁺ and Al-tolerance genes in Arabidopsis. Knocking out the gene encoding the STOP1-like protein decreased the Al tolerance of P. patens. Together, our results strongly suggest that transcriptional regulation by STOP1-like proteins is evolutionarily conserved among land plants and that it confers the ability to survive in acid soils through the transcriptional regulation of Al- and H⁺-tolerance genes.

External validation of risk classification in patients with docetaxel-treated castration-resistant prostate cancer.

BACKGROUND: Castration-resistant prostate cancer (CRPC) patients have poor prognoses, and docetaxel (DTX) is among the few treatment options. An accurate risk classification to identify CRPC patient groups for which DTX would be effective is urgently warranted. The Armstrong risk classification (ARC), which classifies CRPC patients into 3 groups, is superior; however, its usefulness remains unclear, and further external validation is required before clinical use. This study aimed to examine the clinical significance of the ARC through external validation in DTX-treated Japanese CRPC patients. METHODS: CRPC patients who received 2 or more DTX cycles were selected for this study. Patients were classified into good-, intermediate-, and poor-risk groups according to the ARC. Prostate-specific antigen (PSA) responses and overall survival (OS) were calculated and compared between the risk groups. A multivariate analysis was performed to clarify the relationship between the ARC and major patient characteristics. RESULTS: Seventy-eight CRPC patients met the inclusion criteria. Median PSA levels at DTX initiation was 20 ng/mL. Good-, intermediate-, and poor-risk groups comprised 51 (65%), 17 (22%), and 10 (13%) patients, respectively. PSA response rates ≥ 30% and ≥ 50% were 33%, 41%, and 30%, and 18%, 41%, and 20% in the good-, intermediate-, and poor-risk groups, respectivcixely, with no significant differences (p = 0.133 and 0.797, respectively). The median OS in the good-, intermediate-, and poor-risk groups were statistically significant (p < 0.001) at 30.1, 14.2, and 5.7 months, respectively. A multivariate analysis revealed that the ARC and PSA doubling time were independent prognostic factors. CONCLUSIONS: Most of CRPC patients were classified into good-risk group according to the ARC and the ARC could predict prognosis in DTX-treated CRPC patients. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) number, UMIN000011969.

Optimal interval for delayed retrieval surgery with reciprocating morcellators after enucleation of giant prostatic hyperplasia in holmium laser enucleation of the prostate.

Objective: The aim of this research was to evaluate the efficiency of reciprocating morcellation for removing giant benign prostatic hyperplasia during holmium laser enucleation of the prostate, investigate whether performing morcellation as a two-stage procedure improves tissue retrieval efficiency, and seek to determine the optimal interval between the two surgeries. Methods: This study included nine cases of holmium laser enucleation of the prostate with an enucleated prostate weight exceeding 200 g, indicative of substantial prostate enlargement. Morcellation was performed on Day 0 (n=4), Day 4 (n=1), Day 6 (n=1), and Day 7 (n=3). The intervals were compared regarding the morcellation efficiency, beach ball presence, and pathology. Results: The mean estimated prostate volume was 383 (range 330-528) mL; the median enucleation weight was 252 (interquartile range [IQR] 222, 342) g; and the median enucleation time was 83 (IQR 62, 100) min. The mean morcellation efficiency was 1.44 (SD 0.55) g/min on Day 0 and 13.69 (SD 2.46) g/min on day 7. The morcellation efficiency was 4.15 g/min and 10.50 g/min on Day 4 and Day 6, respectively, with significantly higher in the two-stage group compared to one-stage group (11.0 g/min vs. 1.5 g/min; p=0.014). Efficiency was strongly correlated with intervals (p<0.001); the incidences of beach balls were 100% (4/4) and 60% (3/5) in the immediate and two-stage surgery groups, respectively. Conclusion: The efficiency of two-stage morcellation with reciprocating morcellators was highly related to the postoperative interval, with the maximum efficiency reached on Day 7.

Hand-foot skin reaction is associated with the clinical outcome in patients with metastatic renal cell carcinoma treated with sorafenib.

BACKGROUND: To elucidate whether Hand-Foot skin reaction could become a biomarker of clinical outcome in patients with metastatic renal cell carcinoma treated with sorafenib, we retrospectively examined the association between the Hand-Foot skin reaction and the clinical outcome in metastatic renal cell carcinoma patients treated with sorafenib. METHODS: Thirty-six Japanese metastatic renal cell carcinoma patients treated with sorafenib were enrolled and divided into the groups with or without Hand-Foot skin reaction. Patient characteristics, best tumor response, progression-free survival and adverse events were investigated and compared between these two groups. RESULTS: A sorafenib-induced Hand-Foot skin reaction in metastatic renal cell carcinoma patients was observed at a significantly higher rate in patients in the favorable-risk group in the Memorial Sloan-Kettering Cancer Center risk classification, and with Eastern Cooperative Oncology Group Performance Status of one or less, prior nephrectomy, higher hemoglobin, lower lactate dehydrogenase and lower C-reactive protein. The mean best tumor response was significantly better in the group with Hand-Foot skin reaction (-16.7%) than that in the group without it (17.9%; P < 0.001). The median progression-free survival was significantly longer in the group with Hand-Foot skin reaction (4.6 months) than that in the group without it (1.5 months; P = 0.002). In multivariate analysis, only Hand-Foot skin reaction was shown to be a predictive factor of progression-free survival (hazard ratio 0.312, P = 0.010). CONCLUSIONS: A sorafenib-induced Hand-Foot skin reaction in metastatic renal cell carcinoma patients emerged at a significantly higher rate in patients in the favorable-risk group in the Memorial Sloan-Kettering Cancer Center risk classification and was significantly associated with best tumor response and progression-free survival, suggesting that Hand-Foot skin reaction might be an independent predictive factor for clinical outcome in metastatic renal cell carcinoma patients treated with sorafenib.

Epistatic interactions among multiple copies of FLC genes with naturally occurring insertions correlate with flowering time variation in radish.

Brassicaceae crops, which underwent whole-genome triplication during their evolution, have multiple copies of flowering-related genes. Interactions among multiple gene copies may be involved in flowering time regulation; however, this mechanism is poorly understood. In this study, we performed comprehensive, high-throughput RNA sequencing analysis to identify candidate genes involved in the extremely late-bolting (LB) trait in radish. Then, we examined the regulatory roles and interactions of radish FLOWERING LOCUS C (RsFLC) paralogs, the main flowering repressor candidates. Seven flowering integrator genes, five vernalization genes, nine photoperiodic/circadian clock genes and eight genes from other flowering pathways were differentially expressed in the early-bolting (EB) cultivar 'Aokubinagafuto' and LB radish cultivar 'Tokinashi' under different vernalization conditions. In the LB cultivar, RsFLC1 and RsFLC2 expression levels were maintained after 40 days of cold exposure. Bolting time was significantly correlated with the expression rates of RsFLC1 and RsFLC2. Using the EB × LB F2 population, we performed association analyses of genotypes with or without 1910- and 1627-bp insertions in the first introns of RsFLC1 and RsFLC2, respectively. The insertion alleles prevented the repression of their respective FLC genes under cold conditions. Interestingly, genotypes homozygous for RsFLC2 insertion alleles maintained high RsFLC1 and RsFLC3 expression levels under cold conditions, and two-way analysis of variance revealed that RsFLC1 and RsFLC3 expression was influenced by the RsFLC2 genotype. Our results indicate that insertions in the first introns of RsFLC1 and RsFLC2 contribute to the late-flowering trait in radish via different mechanisms. The RsFLC2 insertion allele conferred a strong delay in bolting by inhibiting the repression of all three RsFLC genes, suggesting that radish flowering time is determined by epistatic interactions among multiple FLC gene copies.

RhoC and guanine nucleotide exchange factor Net1 in androgen-unresponsive mouse mammary carcinoma SC-4 cells and human prostate cancer after short-term endocrine therapy.

BACKGROUND: Endocrine resistance is a critical issue in managing patients with prostate cancer. This study is undertaken to search for a potential molecular target connected with this process using a model system of androgen-dependent and androgen-unresponsive SC-3 and SC-4 cells. METHODS: Expression profiles, actin stress fiber organization, and the levels of activated Rho GTPases were compared between SC-4 and SC-3 cells using an oligonucleotide microarray, phalloidin staining, and a Rho activation assay. The cell viability was analyzed with a Rho inhibitor or by stable transfection with either a dominant-negative (DN) form of RhoC or a mutant form of NET1 (mutNET1). The expressions of RhoC, NET1, and epithelial-mesenchymal transition (EMT) markers were immunohistochemically analyzed in human prostate cancer specimens after short-term endocrine therapy and in an untreated condition. RESULTS: SC-4 cells exhibited mesenchymal phenotypes with activation of Rho signals. Treatment with a Rho inhibitor suppressed the cell viability in SC-4 cells, but not in SC-3 cells. The cell viability of SC-4 cells stably expressing DN-RhoC and mutNET1 was also attenuated. In the immunohistochemical analysis, NET1 and the EMT marker of N-cadherin were expressed at higher levels in prostate cancers after short-term endocrine therapy than in untreated tumors, and RhoC expression was maintained after short-term endocrine therapy. CONCLUSIONS: Rho signaling is involved in the cell survival of SC-4 cells. The higher expressions of RhoC and NET1 in human prostate cancers after short-term endocrine therapy suggest that RhoC and NET1 may become therapeutic targets during endocrine therapy.

Docetaxel with or without estramustine for estramustine refractory castration-resistant prostate cancer: a single institution experience.

BACKGROUND: The significance of combination of docetaxel (DTX) with estramustine phosphate (EMP) in castration-resistant prostate cancer (CRPC) patients remains unclear. In this study, we aimed to retrospectively evaluate the efficacy and toxicity of DTX with or without EMP and to elucidate the significance of DTX and EMP combination therapy in Japanese EMP-refractory CRPC patients. METHODS: To compare the efficacy and toxicity of DTX and EMP, we divided CRPC patients, who were confirmed to be resistant to EMP, into the following two groups: group D (n = 28), which included patients treated with DTX (60 mg/m2, once in every four weeks) alone, and group DE (n = 33), which included patients treated with a combination of DTX (60 mg/m2, once in every four weeks) and EMP (twice daily oral administration at 280 mg). RESULTS: Prostate specific antigen (PSA) response (> 50% decline in PSA) was observed in six patients (21%) in group D and eight patients (24%) in group DE. The median time to progression (TTP) was 12.0 months and 6.2 months and the median overall survival (OS) was 26.4 months and 24.3 months in group D and DE, respectively. There was no statistical difference between the two groups in terms of PSA response, TTP, and OS. The incidence of adverse events of grade 3/4 was low in both the groups, and there was no statistical difference between the two groups. CONCLUSIONS: Although treatment with DTX at 60 mg/m2 was effective and highly tolerated in EMP-refractory Japanese CRPC patients, the DTX and EMP combination therapy might not exhibit any survival benefit for CRPC patients.

Peritoneal invasion of prostate cancer directly confirmed during robot-assisted radical prostatectomy.

Introduction: Several studies have been published on direct rectal invasion in patients with advanced metastatic prostate cancer, but few have directly confirmed intraoperative invasion of prostate cancer into the peritoneum. Case presentation: We report the case of a 73-year-old man with prostate cancer who exhibited peritoneal invasion during robot-assisted radical prostatectomy. His prostate-specific antigen level fell to 0.38 ng/mL after surgery; he was therefore prescribed radiation and androgen-deprivation therapies that controlled the cancer for more than 1 year. Conclusions: We encountered a case showing direct peritoneal invasion of prostate cancer during robot-assisted radical prostatectomy. If invasion of the seminal vesicle is suspected, the vesicorectal fossa should be examined during robot-assisted radical prostatectomy. Preoperative confirmation by diffusion magnetic resonance imaging of the peritoneum is also useful.