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In Japanese clinical practice, more patients with high-risk metastatic hormone-naïve prostate cancer receive androgen deprivation therapy (ADT) plus androgen receptor signalling inhibitors or docetaxel than those receiving ADT alone or combined androgen blockade, the former of which was associated with a more favourable prostate-specific antigen response rate and better progression-free survival, time to castrate-resistant prostate cancer, and overall survival.

Anthrylene- and ferrocenoyl-assisted composite fabrication was achieved between visible-light absorbing anthrylene- and ferrocenoyl-substituted acetylenic dyes and single-wall carbon nanotubes (SWCNTs). The composite formation was confirmed via UV-Vis, Raman, mass, and XPS spectra analyses. In the UV-Vis absorption spectrum, the resulting dye-SWCNT composites showed bathochromic shifts ascribable to the p-p interaction. One-pot fabrication of the composite was also accomplished via Cu-catalyzed dimerization of anthrylene- and ferrocenoyl-substituted terminal ethyne and the subsequent adsorption of the resulting butadiyne dye to SWCNT. We confirmed that the dye-SWCNT composite dispersed in water by using amphiphilic poly(amidoamine)dendrimer could transfer an electron from 1-benzyl-1,4-dihydronicotinamide (BNAH) to methyl viologen dichloride (MV2+) upon irradiation with visible light (>422 nm).The anthrylene- and ferrocenoyl-substituted acetylenic dyes were successfully adsorbed onto the exterior surface of single-wall carbon nanotube (SWCNT) to form the acetylenic dye-SWCNT composite. When visible light (>422 nm) was irradiated to the dye-SWCNT composite that was dispersed in water by using amphiphilic poly(amidoamine)dendrimer, continuous electron transfer from 1-benzyl-1,4-dihydronicotinamide (BNAH) to methyl viologen dichloride (MV2+) was observed.

Objectives: Systematic regional lymph node dissection (LND) combined with radical nephroureterectomy (RNU) has been reported to improve the outcomes of upper tract urothelial carcinoma (UTUC) patients. The objective of the present study was to assess the prognostic outcomes of UTUC patients undergoing systematic regional LND combined with RNU.Patients and methods: We conducted a retrospective evaluation of prognostic outcomes of 68 consecutive UTUC patients treated with RUN and systematic regional LND.Results: The median durations of recurrence-free survival (RFS) and overall survival (OS) were 45 and 166 months, respectively. Univariate analyses of several parameters showed that despite the lack of a significant predictor for RFS, the presence of lymph node metastasis correlated with poor OS.Conclusion: These results suggest that comparatively favorable outcomes are achievable in UTUC patients by RNU and systematic regional LND; however, special attention is needed for patients with nodal involvement even after systematic regional LND due to the adverse impact of this factor on OS.

Optimal drug selection for metastatic hormone-sensitive prostate cancer (mHSPC) remains unclear. We therefore assessed the clinical outcomes of mHSPC treated with new-generation androgen receptor pathway inhibitors (ARSIs) and identified risk factors associated with the prognosis of mHSPC.

To date, no studies have compared the treatment outcomes of second-line therapies in patients with metastatic clear cell renal cell carcinoma (ccRCC). This study retrospectively evaluated the efficacy of cabozantinib and axitinib as second-line treatments in patients with metastatic ccRCC who previously received immune-oncology combination therapy.

Physical modifications of single-walled carbon nanotubes (SWCNTs) with fullerodendrons, followed by complexation with RuCl3leads to the formation of CNT-photocatalysts that exhibit high quantum yields (QY = 12.8%) for the production of H2from water, even under illumination with NIR light (λirr= 1005 nm) in the presence of sacrificial donor. A Z-scheme photocatalytic system, consisting of such a CNT-photocatalyst, BiVO4, and [Co(bpy)3]3+/2+shows a production of H2(17 µmol/h) and O2(5.5 µmol/h) under illumination from a solar simulator (AM-1.5) with a solar-to-hydrogen (STH) efficiency of 0.089%.Physical modifications of single-walled carbon nanotubes (SWCNTs) with fullerodendrons, followed by complexation with RuCl3leads to the formation of CNT-photocatalysts that act as H2evolution photocatalysts (HEPs). A Z-scheme photocatalytic system, consisting of such a CNT-photocatalyst, BiVO4, and [Co(bpy)3]3+/2+shows a production of H2(17 µmol/h) and O2(5.5 µmol/h) under illumination from a solar simulator (AM-1.5) with a solar-to-hydrogen (STH) efficiency of 0.089%.

The incidence of prostate cancer in Japan continues to increase, necessitating the continued development of effective therapies and strategies. Recent advances in treatments have improved the prognosis of metastatic disease and highlighted the importance of treating bone metastases to reduce the incidence of skeletal complications and improve patients’ quality of life. With the increasing number of treatment options that have become available, including bone-targeted therapy with the alpha emitter radium-223 dichloride (Ra-223), Japanese clinicians are faced with making difficult decisions on the choice of optimal treatment strategy. In such situations, guidance based on expert opinions can be beneficial. A panel meeting of 27 Japanese experts in the management of prostate cancer was held to share opinions and to establish consensus recommendations on key clinical questions. Panelists were asked to vote on more than 40 questions pertinent to prostate cancer, and the answers helped guide a comprehensive discussion. The panel reached a consensus on key topics related to the optimal treatment strategy for Ra-223 therapy, namely, that patients with symptomatic, metastatic castration-resistant prostate cancer (CRPC) would benefit most from the use of this agent and that this treatment therapy should be provided before chemotherapy. Other topics that achieved consensus included: monitoring for osteoporosis and providing treatment if necessary during androgen deprivation therapy; performing magnetic resonance imaging in the presence of discrepancies in bone scintigram and computed tomography scans; monitoring alkaline phosphatase during CRPC treatment; using osteoclast-targeting in patients with CRPC with bone metastases; and using osteoclast-targeted agents combined with Ra-223. These consensus recommendations and the updated information which became available subsequent to the panel meeting included here provide useful information for clinicians to aid in designing optimal treatment strategies for their patients. Bayer Yakuhin Ltd.

Multi-walled carbon nanotube (MWCNT)/dendrimer sheet scaffolds, i.e., dendrimers attached to the surface of MWCNT buckypaper, were fabricated, and a hydroxyapatite (HAp) coating prepared on dendrimer-modified buckypaper using an alternate soaking process (ASP) is described. The amount of the HAp that is retained on the surface of the MWCNT/dendrimer sheet scaffolds depends on the modification method; i.e., surface modification performed after the formation of the buckypaper is much more effective in producing MWCNT/HAp hybrid materials than surface modification prior to the formation of the buckypaper. Moreover, biomimetic crystallization of calcium phosphate on buckypaper in simulated body fluid (SBF) was carried out. TEM analysis of the resulting MWCNT/dendrimer sheet scaffolds revealed that the MWCNT backbone was covered with scaly crystals. Multi-walled carbon nanotube (MWCNT)/dendrimer sheet scaffolds, i.e., dendrimers attached to the surface of MWCNT buckypaper, were fabricated, and a hydroxyapatite (HAp) coating prepared on dendrimer-modified buckypaper using an alternate soaking process (ASP) is described. The amount of the HAp that is retained on the surface of the MWCNT/dendrimer sheet scaffolds depends on the dendrimer contents. Moreover, biomimetic crystallization of calcium phosphate on buckypaper in simulated body fluid (SBF) was carried out. TEM analysis of the resulting MWCNT/dendrimer sheet scaffolds revealed that the MWCNT backbone was covered with scaly crystals.

To clarify the role of serotonin (5-HT) in the prevention of stress urinary incontinence (SUI) during sneezing, we investigated the effect of intraperitoneal application of p-chlorophenylalanine (PCPA; a serotonin synthesis inhibitor) and intravenous application of CP-809101 (a 5-HT2Cagonist) or LP44 (a 5-HT7agonist) using female rats, in which the neurally evoked continence reflex during sneezing was examined. Amplitudes of urethral pressure response during sneezing (A-URS), urethral baseline pressure (UBP) at the middle urethra, and sneeze-induced leak point pressure (S-LPP) were measured in normal female adult rats with or without drug administration. PCPA decreased A-URS by 35.1 cmH2O and UBP by 13.3 cmH2O compared with normal rats. In PCPA-administrated rats, CP-809101 increased A-URS by 24.1 cmH2O and UBP by 15.1 cmH2O, and LP44 also increased A-URS by 20.6 cmH2O and UBP by 11.4 cmH2O compared with rats treated with PCPA alone. SUI was observed with S-LPP of 40.1 cmH2O in PCPA-administrated rats, in which CP-809101 and LP44 increased S-LPP by 28.0 and 15.2 cmH2O, respectively, compared with rats treated with PCPA alone. The effects of CP-809101 and LP44 were antagonized by SB-242084 (a selective 5-HT2Cantagonist) and SB-269970 (a selective 5-HT7antagonist), respectively. These results indicate that activation of 5-HT receptors enhances the active urethral closure reflex during sneezing, at least in part via 5-HT2Cand 5-HT7receptors.

The present study included 222 patients with metastatic castration-resistant prostate cancer. Of the 222 patients, 108 and 114 received an alternative androgen receptor-axis-targeted agent (ARATA) or docetaxel, respectively, after the failure of initial ARATA. We found that the oncologic outcomes, including the response rate, progression-free survival, and overall survival, were significantly superior in the 114 patients receiving docetaxel compared with those of the 108 patients receiving ARATA.

The investigation of the efficacy of sequential therapies with novel androgen receptor-axis-targeted (ARAT) agents for docetaxel-naïve patients with metastatic castration-resistant prostate cancer revealed the superiority of the abiraterone-to-enzalutamide sequence over the reverse sequence regarding combined prostate-specific antigen progression-free survival, but not overall survival. Therefore, despite the occurrence of cross-resistance with either sequence, ARAT therapy with the abiraterone-to-enzalutamide sequence might be preferable.

The comparative assessment of clinical outcomes between abiraterone acetate and enzalutamide in Japanese patients with docetaxel-naive metastatic castration-resistant prostate cancer showed acceptable efficacy and tolerability for both agents. However, the prostate-specific antigen response and adverse event profile appeared to be significantly advantageous in the enzalutamide and abiraterone acetate group, respectively.

The assessment of efficacy in novel androgen receptor-axis-targeted (ARAT) therapies with abiraterone acetate and/or enzalutamide for docetaxel-naive metastatic castration-resistant prostate cancer showed common occurrence of cross-resistance between the ARAT agents, irrespective of the use of taxanes between these agents. Therefore, following the failure of either ARAT agent, it might be preferable to avoid the sequential administration of another ARAT agent.

Encouraging data, including efficacy, safety, and quality of life, could be achieved in Japanese patients with metastatic renal-cell carcinoma (mRCC) who received axitinib as a second-line agent in a real-world clinical setting. The introduction of axitinib as a standard of care may thus be strongly recommended for Japanese mRCC patients after the failure of first-line systemic therapy.

We succeeded in the first isolation of a single pure regioisomer of a C70–acene monoadduct. 1,9-Diels–Alder monoadducts of C70with pentacene derivatives were obtained by not only the Diels–Alder reaction but also a one-pot reaction using stable dihydropentacene derivatives, 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), and C70. The X-ray crystallographic study of a single pure regioisomer 2bconfirmed positions of the linkage between C70and acenes for the first time, and revealed unique columnar stacks.

Several adverse events (AEs) are known to be commonly observed during treatment with different tyrosine kinase inhibitors (TKIs) in patients with metastatic renal cell carcinoma (mRCC) patients. However, no significant correlation appears present in the profiles of such AEs between first- and second-line TKI therapies. Therefore, a second-line targeted agent for patients with mRCC could be selected irrespective of the AE profile during first-line TKI therapy.

Thiophene-based dyes bearing two ferrocenylcarbonyl groups were obtained from a short synthesis involving direct arylations of the thiophene rings. A subsequent thionation of the carbonyl groups resulted in the formation of new thiophene-based dyes bearing two ferrocenylthiocarbonyl groups. These dyes absorb in a wide range of the visible spectrum due to their π–π* and d–π* transitions, and show a remarkable red-shift of the absorption band relative to their carbonyl analogues without increasing the molecular size.New thiophene-based dyes bearing two ferrocenylthiocarbonyl groups were obtained from a short synthesis based on direct arylation reactions at the thiophene rings. The dyes absorb in a wide range of the visible spectrum due to their π–π* and d–π* transitions. The thionation of the carbonyl groups resulted in a remarkable red-shift of the absorption band without increasing the molecular size.

[3]Radialenes: 4,5,6‐Tris(2,4,6‐tri‐tert‐butylphenyl)phospha[3]radialene has been synthesized (see picture). The compound can be easily handled in air under ambient conditions, despite the [3]radialene moiety containing PC bonds, and exhibits red‐shifted absorption as well as high electron‐accepting ability. The unique electronic properties are brought about by the synergistic effect of the [3]radialene framework and the phosphorus substitution.

[3]Radialene: Die synthetisierte Titelverbindung (siehe Bild) kann trotz ihrer [3]Radialen‐Einheit mit PC‐Bindungen unter Umgebungsbedingungen problemlos an der Luft gehandhabt werden und zeigt eine rotverschobene Absorption sowie ein hohes Elektronenakzeptorvermögen. Der Ursprung dieser ungewöhnlichen elektronischen Eigenschaften ist eine Synergie zwischen dem [3]Radialen‐Gerüst und der Phosphorsubstitution.

2-(2,4,6-Tri-tert-butylphenyl)-1-phosphaethyne was allowed to react with trimethylsilyldiazomethane derivatives to afford the corresponding 1,2,4-diazaphospholes via [2+3] cycloaddition followed by H/SiMe3 migration, in spite of the steric encumbrance of the substrates. The aromatic character of 1,2,4-diazaphosphole is indicated by the NMR spectroscopic data and the X-ray structure analysis as well as by theoretical calculation to confirm the planar delocalized ring skeleton. The crystal structure of the obtained 1,2,4-diazaphospholes showed remarkable hydrogen bonding character in relation to molecular aggregation due to the presence of bulky aryl groups. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

To achieve the goals of engineering large complex tissues, and possibly internal organs, vascularization of the regenerating tissue is essential. To maintain the initial volume after implantation of regenerated tissue, improved vascularization is considered to be important. Recent advances in understanding the process of blood vessel growth has offered significant tools for the neovascularization of bioengineered tissues and therapeutic angiogenesis. Several angiogenic growth factors including vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and hepatocyte growth factor (HGF) were used for vascularization of ischemic tissues. Other approaches such as prevascularization of the scaffold, prior to cell seeding, and incorporation of endothelial cells in the bioengineered tissue showed encouraging results. In this article, we will review recent advances in angiogenic growth factors, and discuss the role of these growth factors and endothelial cells in therapeutic angiogenesis and tissue engineering.

Androgen-independent (AI) progression remains the main obstacle to improving the survival of patients with prostate cancer. Recently, we characterized changes in gene expression profile during AI progression in the prostate cancer model systems as well as the clinical specimens, and identified several genes, including bcl-2, bcl-xL, clusterin, insulin-like growth factor binding protein (IGFBP)-2, IGFBP-5 and heat shock protein 27, that are involved in the signal transduction pathways mediating resistance to various kinds of apoptotic stimuli. We then showed the efficacy of inactivating such antiapoptotic genes using antisense (AS) oligodeoxynucleotides (ODNs) to delay AI progression after androgen withdrawal. We further demonstrated the synergistic effects of AS ODN therapy combined with several treatments, such as cytotoxic chemotherapy, radiation and other molecular targeting therapies. In this review, we attempted to summarize the progress we have made in the field of AS ODN strategy against prostate cancer, and to discuss the preliminary data of the recently completed phase I clinical trials using AS ODNs as well as the future prospects of this therapy. The findings presented in this review may help clarify the significance of AS ODN therapy targeting relevant genes as an attractive alternative to conventional strategies for prostate cancer.

This review summarise the authors’ recent experience in the development of antisense (AS) oligodeoxynucleotide (ODN) therapy that targets a cytoprotective gene, clusterin, for the treatment of prostate cancer. The acquisition of resistance to a wide variety of proapototic stimuli was initially demonstrated by introducing the clusterin gene into prostate cancer cells. Furthermore, silencing clusterin expression using AS ODN synergistically enhanced the effects of several conventional therapeutic modalities through the effective induction of apoptosis in prostate cancer xenograft models. Based on these outcomes, Phase I clinical trials were conducted using AS clusterin ODN incorporating 2′-O-(2-methoxy)ethyl-gapmer backbone (OGX-011), and the optimal dose of OGX-011 capable of inducing ≤ 90% suppression of clusterin in human prostate cancer tissue was determined. Collectively, these findings suggest the utility of inactivating clusterin function using AS ODN technology as a novel therapeutic strategy for prostate cancer treatment. There have been four kinds of Phase II studies that have begun to further evaluate the efficacy of OGX-011 in patients with prostate, breast and lung cancers.

Despite remarkable progress in therapeutic options for the management of bladder cancer, it remains a challenge for urologists to achieve successful outcomes in the treatment of both superficial and invasive bladder cancers. In this review, recent advances in the field of antisense oligodeoxynucleotide therapy targeting several genes playing functionally important roles in the progression and recurrence of bladder cancer are summarized. Data showing the synergistic antitumor activities of antisense oligodeoxynucleotide therapy, combined with several treatments, including cytotoxic chemotherapy, radiation and other molecular targeting therapies, are also presented. Finally, the future direction of antisense oligodeoxynucleotide therapy in the therapeutic strategy of bladder cancer is dicussed. These findings may help clarify the significance of antisense oligodeoxynucleotide therapy as an attractive alternative to conventional strategies.

In mixing 2,4,6‐tris(2,4,6‐tri‐tert‐butylphenyl)‐1,3,6‐triphosphafulvene with alkyllithium compounds and acetic acid, both of nucleophilic alkylation and electrophilic protonation occurred at the exosp2‐phosphorus atoms to afford [2,4‐bis(2,4,6‐tri‐tert‐butylphenyl)‐1,3‐diphosphacyclopentadienylidene](alkyl)(2,4,6‐tri‐tert‐butylphenyl)phosphoranes which are phosphorus ylides that bear a PH bond. A phosphorus ylide bearing both PH and PF bonds was obtained by reaction of 2,4,6‐tris(2,4,6‐tri‐tert‐butylphenyl)‐1,3,6‐triphosphafulvene with hydrogen tetrafluoroborate, and the structure was determined by X‐ray crystallography. Both PC double bond and P+C−zwitterionic character was indicated by the metric parameters. The isolated phosphorus ylide bearing a PH bond, [2,4‐bis(2,4,6‐tri‐tert‐butylphenyl)‐1,3‐diphosphacyclopentadienylidene](2,4,6‐tri‐tert‐butylphenyl)phosphorane, showed no isomerization by H‐migration to the corresponding phosphinodiphospholes, probably due to the π‐accepting ability of the unsaturated PC bonds and aromaticity of the C3P2ring. The ylide structure and aromaticity of 2,4‐diphosphacyclopenta‐2,4‐dienylidenephosphorane was characterized by theoretical calculations. In addition, the regioselective protonation of the lithiated phosphinodiphospholes generated from the 1,3,6‐triphosphafulvene is discussed.

Bacillus Calmette Guerin (BCG) immunotherapy has anti‐tumorigenic effects against bladder cancer. To improve the efficacy of BCG therapy, we introduced the gene encoding the 65 kDa heat shock protein (hsp) of Mycobacterium tuberculosisinto a mouse malignant melanoma cell line (B16). An expression vector harboring the 65 kDa antigen gene was transfected into B16 using Lipofectamine, then expression of the antigen was confirmed by RT‐PCR and Western blotting. Several cell lines expressing 65 kDa antigen were established (B16/65kDa). We also established a control cell line transfected with the vector alone (B16/con). All cell lines (B16, B16/con, B16/65kDa) were injected intraperitoneally into syngeneic mice with or without BCG prior immunization and the development of tumor ascites was examined. To analyze the mechanism of the anti‐tumor effect, CD4 T cells or CD8 T cells were depleted in vivoby administering the corresponding monoclonal antibody. B16/65kDa expressed the 65 kDa hsp of M. tuberculosis. The tumor growth of B16/65kDa was slightly retarded in naive mice, but significantly inhibited by BCG. The anti‐tumor effect was totally abrogated in mice deficient in CD4 T cells, suggesting that CD4 T cells are involved in this process. The 65 kDa hsp of M. tuberculosiswas expressed after gene transduction in a malignant melanoma cell line and significantly enhanced the anti‐tumor effect of BCG immunotherapy. CD4 T cells play an important role in this anti‐tumor effect.

TNP-470 (O-(chloroacetylcarbamoyl)fumagillol) is a potent inhibitor of angiogenesis that was reported to enhance synergistically the antitumor effects of cytotoxic agents. We evaluated the effectiveness of combined treatment with TNP-470 and gemcitabine in vitro and in vivo using highly metastatic human bladder cancer KoTCC-1 cells.

We evaluated the effects of the over expression of CD44v8–10, one of the high molecular form of CD44, on the malignant potential of UM-UC-3 human bladder cancer cells in vitro and in vivo.

We evaluated the significance of oxidative DNA damage in patients with prostate cancer based on the measurement of urinary 8-OHdG (8-hydroxy-2′-deoxyguanosine) and analyzed changes in urinary 8-OHdG before and after initial treatment.

We investigated whether antisense (AS) oligodeoxynucleotide (ODN) targeting the clusterin gene enhances the cytotoxic effect of gemcitabine in human bladder cancer KoTCC-1 cells in vitro and in vivo, and evaluated the usefulness of the combined administration of AS clusterin ODN and gemcitabine using an intraperitoneal tumor cell injection model.

Neutron production via 4He breakup and p(p, np+)p is considered in the innermost region of an accretion disk surrounding a Kerr black hole. These reactions occur in a plasma in Wien equilibrium, where (radiatively produced) pair production equals annihilation. Cooling of the disk is assumed to be due to unsaturated inverse Comptonization of external soft photons and to the energy needed to ignite both nuclear reactions. Assuming matter composition of 90% H and 10% He, we show that, close to the border of this region, neutron production is essentially from 4He breakup. Close to the horizon, the contribution from p(p, np+)p to the neutron production is comparable to that from the breakup. We show that the viscosity generated by the collisions of the accreting matter with the neutrons may drive stationary accretion, for accretion rates below a critical value. In this case, the solution to the disk equations is double-valued, and for both solutions protons outnumber the pairs. Our results apply whenever M17/M < 1.74. We suggest that these solutions may mimic the states of high and low luminosity observed in Cygnus X-1 and related sources. This could be explained either by the coupling of thermal instability to the peculiar behavior of the viscosity parameter a with the ion temperature that may intermittently switch accretion off, or by the impossibility of a perfect tuning for both thermal and pair equilibrium in the disk, a fact that forces the system to undergo a kind of limit cycle behavior around the upper solution.