GM-CSF Promotes the Survival of Peripheral-Derived Myeloid Cells in the Central Nervous System for Pain-Induced Relapse of Neuroinflammation.

We recently discovered a (to our knowledge) new neuroimmune interaction named the gateway reflex, in which the activation of specific neural circuits establishes immune cell gateways at specific vessel sites in organs, leading to the development of tissue-specific autoimmune diseases, including a multiple sclerosis (MS) mouse model, experimental autoimmune encephalomyelitis (EAE). We have reported that peripheral-derived myeloid cells, which are CD11b+MHC class II+ and accumulate in the fifth lumbar (L5) cord during the onset of a transfer model of EAE (tEAE), play a role in the pain-mediated relapse via the pain-gateway reflex. In this study, we investigated how these cells survive during the remission phase to cause the relapse. We show that peripheral-derived myeloid cells accumulated in the L5 cord after tEAE induction and survive more than other immune cells. These myeloid cells, which highly expressed GM-CSFRα with common ß chain molecules, grew in number and expressed more Bcl-xL after GM-CSF treatment but decreased in number by blockade of the GM-CSF pathway, which suppressed pain-mediated relapse of neuroinflammation. Therefore, GM-CSF is a survival factor for these cells. Moreover, these cells were colocalized with blood endothelial cells (BECs) around the L5 cord, and BECs expressed a high level of GM-CSF. Thus, GM-CSF from BECs may have an important role in the pain-mediated tEAE relapse caused by peripheral-derived myeloid cells in the CNS. Finally, we found that blockade of the GM-CSF pathway after pain induction suppressed EAE development. Therefore, GM-CSF suppression is a possible therapeutic approach in inflammatory CNS diseases with relapse, such as MS.

DDX6 is involved in the pathogenesis of inflammatory diseases via NF-κB activation.

The IL-6 amplifier was originally discovered as a mechanism for the enhanced activation of NF-κB in non-immune cells. In the IL-6 amplifier, IL-6-STAT3 and NF-κB stimulation is followed by an excessive production of IL-6, chemokines, and growth factors to develop chronic inflammation preceding the development of inflammatory diseases. Previously, using a shRNA-mediated genome-wide screening, we found that DEAD-Box Helicase 6 (DDX6) is a candidate positive regulator of the amplifier. Here, we investigate whether DDX6 is involved in the pathogenesis of inflammatory diseases via the IL-6 amplifier. We found that DDX6-silencing in non-immune cells suppressed the NF-κB pathway and inhibited activation of the IL-6 amplifier, while the forced expression of DDX6 enhanced NF-κB promoter activity independent of the RNA helicase activity of DDX6. The imiquimod-mediated dermatitis model was suppressed by the siRNA-mediated gene downregulation of DDX6. Furthermore, silencing DDX6 significantly reduced the TNF-α-induced phosphorylation of p65/RelA and IκBα, nuclear localization of p65, and the protein levels of IκBα. Mechanistically, DDX6 is strongly associated with p65 and IκBα, but not TRADD, RIP, or TRAF2, suggesting a novel function of DDX6 as an adaptor protein in the NF-κB pathway. Thus, our findings demonstrate a possible role of DDX6 beyond RNA metabolism and suggest DDX6 is a therapeutic target for inflammatory diseases.

Bladder cancer risk stratification with the Oncuria 10-plex bead-based urinalysis assay using three different Luminex xMAP instrumentation platforms.

BACKGROUND: No single marker of bladder cancer (BC) exists in urine samples with sufficient accuracy for disease diagnosis and treatment monitoring. The multiplex Oncuria BC assay noninvasively quantifies the concentration of 10 protein analytes in voided urine samples to quickly generate a unique molecular profile with proven BC diagnostic and treatment-tracking utility. Test adoption by diagnostic and research laboratories mandates reliably reproducible assay performance across a variety of instrumentation platforms used in different laboratories. METHODS: We compared the performance of the clinically validated Oncuria BC multiplex immunoassay when data output was generated on three different analyzer systems. Voided urine samples from 36 subjects (18 with BC and 18 Controls) were reacted with Oncuria test reagents in three 96-well microtiter plates on Day 1, and consecutively evaluated on the LED/image-based MagPix, and laser/flow-based Luminex 200 and FlexMap 3D (all xMAP instruments from Luminex Corp., Austin, TX) on Day 2. The BC assay uses magnetic bead-based fluorescence technology (xMAP, Multi-analyte profiling; Luminex) to simultaneously quantify 10 protein analytes in urine specimens [i.e., angiogenin (ANG), apolipoprotein E (ApoE), carbonic anhydrase IX (CA9), CXCL8/interleukin-8 (IL-8), matrix metalloproteinase-9 (MMP-9), matrix metalloproteinase-10 (MMP-10), serpin A1/alpha-1 anti-trypsin (A1AT), serpin E1/plasminogen activator inhibitor-1 (PAI-1), CD138/syndecan-1 (SDC1), and vascular endothelial growth factor-A (VEGF-A)]. All three analyzers quantify fluorescence signals generated by the Oncuria assay. RESULTS: All three platforms categorized all 10 analytes in identical samples at nearly identical concentrations, with variance across systems typically < 5%. While the most contemporary instrument, the FlexMap 3D, output higher raw fluorescence values than the two comparator systems, standard curve slopes and analyte concentrations determined in urine samples were concordant across all three units. Forty-four percent of BC samples registered ≥ 1 analyte above the highest standard concentration, i.e., A1AT (n = 7/18), IL-8 (n = 5), and/or ANG (n = 2), while only one control sample registered an analyte (A1AT) above the highest standard concentration. CONCLUSION: Multiplex BC assays generate detailed molecular signatures useful for identifying BC, predicting treatment responsiveness, and tracking disease progression and recurrence. The similar performance of the Oncuria assay across three different analyzer systems supports test adaptation by clinical and research laboratories using existing xMAP platforms. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov as NCT04564781, NCT03193528, NCT03193541, and NCT03193515.

Computer model of IL-6-dependent rheumatoid arthritis in F759 mice.

The interleukin-6 (IL-6) amplifier, which describes the simultaneous activation of signal transducer and activator of transcription 3 (STAT3) and NF-κb nuclear factor kappa B (NF-κB), in synovial fibroblasts causes the infiltration of immune cells into the joints of F759 mice. The result is a disease that resembles human rheumatoid arthritis. However, the kinetics and regulatory mechanisms of how augmented transcriptional activation by STAT3 and NF-κB leads to F759 arthritis is unknown. We here show that the STAT3-NF-κB complex is present in the cytoplasm and nucleus and accumulates around NF-κB binding sites of the IL-6 promoter region and established a computer model that shows IL-6 and IL-17 (interleukin 17) signaling promotes the formation of the STAT3-NF-κB complex followed by its binding on promoter regions of NF-κB target genes to accelerate inflammatory responses, including the production of IL-6, epiregulin, and C-C motif chemokine ligand 2 (CCL2), phenotypes consistent with in vitro experiments. The binding also promoted cell growth in the synovium and the recruitment of T helper 17 (Th17) cells and macrophages in the joints. Anti-IL-6 blocking antibody treatment inhibited inflammatory responses even at the late phase, but anti-IL-17 and anti-TNFα antibodies did not. However, anti-IL-17 antibody at the early phase showed inhibitory effects, suggesting that the IL-6 amplifier is dependent on IL-6 and IL-17 stimulation at the early phase, but only on IL-6 at the late phase. These findings demonstrate the molecular mechanism of F759 arthritis can be recapitulated in silico and identify a possible therapeutic strategy for IL-6 amplifier-dependent chronic inflammatory diseases.

Gateway reflexes, neuronal circuits that regulate the autoreactive T cells in organs having blood barriers.

Gateway reflexes are neural circuits that maintain homeostasis of the immune system. They form gateways for autoreactive T cells to infiltrate the central nervous system in a noradrenaline-dependent manner despite the blood-brain barrier. This mechanism is critical not only for maintaining organ homeostasis but also for inflammatory disease development. Gateway reflexes can be regulated by environmental or artificial stimuli including electrical stimulation, suggesting that the infiltration of immune cells can be controlled by bioelectronic medicine. In this review, we describe the discovery of gateway reflexes and their future directions with special focus on bioelectronic medicine.

Current trends in the promising immune checkpoint inhibition and radiotherapy combination for locally advanced and metastatic urothelial carcinoma.

Locally advanced and metastatic urothelial carcinoma (UC) remains a challenging malignancy, though several novel therapeutic drugs have been developed in recent years. Over the past decade, immune checkpoint inhibitors (ICI) have shifted the paradigm of therapeutic strategies for UC; however, only a limited number of patients respond to ICI. Since radiotherapy (RT) is widely known to induce systemic immune activation, it may boost the efficacy of ICI. Conversely, RT also causes exhaustion of cytotoxic T cells, and the activation and recruitment of immunosuppressive cells; ICI may help overcome these immunosuppressive effects. Therefore, the combination of ICI and RT has attracted attention in recent years. The therapeutic benefits of this combination therapy and its optimal regimen have not yet been determined through prospective studies. Therefore, this review article aimed to provide an overview of the current preclinical and clinical studies that illustrate the underlying mechanisms and explore the optimization of the RT regimen along with the ICI and RT combination sequence. We also analyzed ongoing prospective studies on ICI and RT combination therapies for metastatic UC. We noted that the tumor response to ICI and RT combination seemingly differs among cancer types. Thus, our findings highlight the need for well-designed prospective trials to determine the optimal combination of ICI and RT for locally advanced and metastatic UC.

MRI/RNA-Seq-Based Radiogenomics and Artificial Intelligence for More Accurate Staging of Muscle-Invasive Bladder Cancer.

Accurate staging of bladder cancer assists in identifying optimal treatment (e.g., transurethral resection vs. radical cystectomy vs. bladder preservation). However, currently, about one-third of patients are over-staged and one-third are under-staged. There is a pressing need for a more accurate staging modality to evaluate patients with bladder cancer to assist clinical decision-making. We hypothesize that MRI/RNA-seq-based radiogenomics and artificial intelligence can more accurately stage bladder cancer. A total of 40 magnetic resonance imaging (MRI) and matched formalin-fixed paraffin-embedded (FFPE) tissues were available for analysis. Twenty-eight (28) MRI and their matched FFPE tissues were available for training analysis, and 12 matched MRI and FFPE tissues were used for validation. FFPE samples were subjected to bulk RNA-seq, followed by bioinformatics analysis. In the radiomics, several hundred image-based features from bladder tumors in MRI were extracted and analyzed. Overall, the model obtained mean sensitivity, specificity, and accuracy of 94%, 88%, and 92%, respectively, in differentiating intra- vs. extra-bladder cancer. The proposed model demonstrated improvement in the three matrices by 17%, 33%, and 25% and 17%, 16%, and 17% as compared to the genetic- and radiomic-based models alone, respectively. The radiogenomics of bladder cancer provides insight into discriminative features capable of more accurately staging bladder cancer. Additional studies are underway.

Association of SNPs in the PAI1 Gene with Disease Recurrence and Clinical Outcome in Bladder Cancer.

PURPOSE: Bladder cancer (BCa) is one of the most common cancer types worldwide and is characterized by a high rate of recurrence. In previous studies, we and others have described the functional influence of plasminogen activator inhibitor-1 (PAI1) in bladder cancer development. While polymorphisms in PAI1 have been associated with increased risk and worsened prognosis in some cancers, the mutational status of PAI1 in human bladder tumors has not been well defined. METHODS: In this study, we evaluated the mutational status of PAI1 in a series of independent cohorts, comprised of a total of 660 subjects. RESULTS: Sequencing analyses identified two clinically relevant 3' untranslated region (UTR) single nucleotide polymorphisms (SNPs) in PAI1 (rs7242; rs1050813). Somatic SNP rs7242 was present in human BCa cohorts (overall incidence of 72%; 62% in Caucasians and 72% in Asians). In contrast, the overall incidence of germline SNP rs1050813 was 18% (39% in Caucasians and 6% in Asians). Furthermore, Caucasian patients with at least one of the described SNPs had worse recurrence-free survival and overall survival (p = 0.03 and p = 0.03, respectively). In vitro functional studies demonstrated that SNP rs7242 increased the anti-apoptotic effect of PAI1, and SNP rs1050813 was related to a loss of contact inhibition associated with cellular proliferation when compared to wild type. CONCLUSION: Further investigation of the prevalence and potential downstream influence of these SNPs in bladder cancer is warranted.

The gateway reflex: breaking through the blood barriers.

We have been studying inflammatory diseases, with a special focus on IL-6, and discovered two concepts related to inflammation development. One is the gateway reflex, which is induced by the activation of specific neural circuits followed by establishing gateways for autoreactive CD4+ T cells to pass through blood barriers toward the central nervous system (CNS) and retina during tissue-specific inflammatory diseases. We found that the formation of these gateways is dependent on the IL-6 amplifier, which is machinery for enhanced NF-κB activation in endothelial cells at specific sites. We have found five gateway reflexes in total. Here, we introduce the gateway reflex and the IL-6 amplifier.

Antitumor effect of WEE1 blockade as monotherapy or in combination with cisplatin in urothelial cancer.

Overcoming cisplatin (CDDP) resistance is a major issue in urothelial cancer (UC), in which CDDP-based chemotherapy is the first-line treatment. WEE1, a G2 /M checkpoint kinase, confers chemoresistance in response to genotoxic agents. However, the efficacy of WEE1 blockade in UC has not been reported. MK-1775, a WEE1 inhibitor also known as AZD-1775, blocked proliferation of UC cell lines in a dose-dependent manner irrespective of TP53 status. MK-1775 synergized with CDDP to block proliferation, inducing apoptosis and mitotic catastrophe in TP53-mutant UC cells but not in TP53-WT cells. Knocking down TP53 in TP53-WT cells induced synergism of MK-1775 and CDDP. In UMUC3 cell xenografts and two patient-derived xenograft lines with MDM2 overexpression, in which the p53/cell cycle pathway was inactivated, AZD-1775 combined with CDDP suppressed tumor growth inducing both M-phase entry and apoptosis, whereas AZD-1775 alone was as effective as the combination in RT4 cell xenografts. Drug susceptibility assay using an ex vivo cancer tissue-originated spheroid system showed correlations with the in vivo efficacy of AZD-1775 alone or combined with CDDP. We determined the feasibility of the drug susceptibility assay using spheroids established from UC surgical specimens obtained by transurethral resection. In conclusion, WEE1 is a promising therapeutic target in the treatment of UC, and a highly specific small molecule inhibitor is currently in early phase clinical trials for cancer. Differential antitumor efficacy of WEE1 blockade alone or combined with CDDP could exist according to p53/cell cycle pathway activity, which might be predictable using an ex vivo 3D primary culture system.

Trp53 Mutation in Keratin 5 (Krt5)-Expressing Basal Cells Facilitates the Development of Basal Squamous-Like Invasive Bladder Cancer in the Chemical Carcinogenesis of Mouse Bladder.

The biological processes of urothelial carcinogenesis are not fully understood, particularly regarding the relationship between specific genetic events, cell of origin, and molecular subtypes of subsequent tumors. N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-induced mouse bladder cancer is widely accepted as a useful model that recapitulates the pathway of human bladder tumorigenesis from dysplasia to invasive cancer via carcinoma in situ. However, the long and variable time of tumorigenesis often hinders efficient preclinical or translational research. We hypothesized that Trp53 mutation in specific types of urothelial cells facilitates efficient development of clinically relevant bladder cancer. Using lineage tracing, we showed that Trp53 mutation in Krt5-expressing cells resulted in more efficient tumorigenesis of mouse muscle-invasive bladder cancer (MIBC) with squamous differentiation compared with Trp53 mutation in Upk2-expressing cells, or wild-type or hemizygous Trp53 in the entire urothelium. Mouse MIBC that developed at 24 weeks of BBN treatment showed morphologic and genetic similarities to the basal squamous subtypes of human MIBC, irrespective of pre-induction of Trp53 mutation or whether the cell of origin was Krt5- or Upk2-expressing cells. Our findings suggest that intermediate cells as well as basal cells also can give rise to basal-like MIBC, with pre-induction of Trp53 mutation accelerating MIBC. Thus, in BBN chemical carcinogenesis, pre-induction of Trp53 mutation in basal cells facilitates efficient modeling of the basal squamous subtype of human MIBC.

Bacillus Calmette-Guérin-unresponsive non-muscle invasive bladder cancer outcomes in patients without radical cystectomy.

BACKGROUND: Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) is a newly defined subtype that is unlikely to benefit from BCG rechallenge. Radical cystectomy is currently recommended for BCG-unresponsive NMIBC; however, a certain proportion of these patients can be managed with treatments other than that. Herein, we conducted a multicenter retrospective study to analyze the clinical outcomes of BCG-unresponsive NMIBC patients who did not receive radical cystectomy. METHODS: Of the 141 BCG-unresponsive NMIBC patients, 94 (66.7%) received treatment except radical cystectomy. Survival outcomes were calculated from the date of diagnosis using the Kaplan-Meier method and compared using the log-rank test. Prognostic factors were identified using the multivariate Cox regression model. This group was further classified into three groups according to the number of risk factors, and survival outcomes were compared. RESULTS: Multivariate analyses identified low estimated glomerular filtration rate (< 45 ml/min/1.73 m2) and large tumor size (≥ 30 mm) before BCG induction as independent poor prognostic factors for progression-free survival and overall survival, while the latter was also an independent factor for cancer-specific survival. The presence of variant histology was an independent poor prognostic factor for overall survival. The high-risk non-cystectomy group showed a significantly poor prognosis for progression-free survival (hazard ratio: 7.61, 95% confidence interval: 2.11-27.5), cancer-specific survival (10.4, 0.54-70.02), and overall survival (8.28, 1.82-37.7). CONCLUSIONS: Our findings suggest that patients with renal impairment and large tumors should undergo radical cystectomy if the complications and intentions of the patients allow so.

Bioshell Calcium Oxide (BiSCaO) Ointment for the Disinfection and Healing of Pseudomonas aeruginosa-Infected Wounds in Hairless Rats.

Bioshell calcium oxide (BiSCaO) possesses deodorizing properties and broad microbicidal activity. This study aimed to investigate the application of BiSCaO ointment for the prevention and treatment of infection in chronic wounds in healing-impaired patients, without delaying wound healing. The bactericidal activities of 0.04, 0.2, 1, and 5 wt% BiSCaO ointment, 3 wt% povidone iodine ointment, and control (ointment only) were compared to evaluate the in vivo disinfection and healing of Pseudomonas aeruginosa-infected wounds in hairless rats. Treatment of the infected wounds with 0.2 wt% BiSCaO ointment daily for 3 days significantly enhanced wound healing and reduced the in vivo bacterial counts compared with povidone iodine ointment and control (no wound cleaning). Although 5 wt% BiSCaO ointment provided the lowest bacterial counts during 3 days' treatment, it delayed wound healing. Histological examinations showed significantly advanced granulation tissue and capillary formation in wounds treated with 0.2 wt% BiSCaO ointment for 3 days compared to wounds treated with the other ointments. This study suggested that using 0.2 wt% BiSCaO ointment as a disinfectant for infected wounds and limiting disinfection to 3 days may be sufficient to avoid the negative effects of BiSCaO on wound repair.

Concentrated Bioshell Calcium Oxide (BiSCaO) Water Kills Pathogenic Microbes: Characterization and Activity.

Bioshell calcium oxide (BiSCaO) exhibits deodorizing properties and broad microbicidal activity. In this study, we examined possible utility of BiSCaO Water for that purpose. BiSCaO Water was prepared by adding 10 wt% BiSCaO to clean water and gently collecting the supernatant in a bottle. The same volume of clean water was gently poured onto the BiSCaO precipitate and the supernatant was gently collected in a bottle; this process was repeated fifty times. The produced BiSCaO Water contained nanoparticles (about 400-800 nm) composed of smaller nanoparticles (100-200 nm), and was colorless and transparent, with a pH > 12.7. In vitro assays demonstrated that BiSCaO Water eliminated more than 99.9% of influenza A (H1N1) and Feline calicivirus, Escherichia coli such as NBRC 3972 and O-157:H7, Pseudomonas aeruginosa, Salmonella, and Staphylococcus aureus within 15 min. We compared BiSCaO Water with the other microbicidal reagents such as ethanol, BiSCaO, BiSCa(OH)2 suspensions, povidone iodine, NaClO, BiSCaO dispersion and colloidal dispersion with respect to deodorization activity and microbicidal efficacy. The results showed that BiSCaO Water was a potent reagent with excellent deodorization and disinfection activities against pathogenic bacteria and viruses (including both enveloped and nonenveloped viruses).

Safety of Concentrated Bioshell Calcium Oxide Water Application for Surface and Skin Disinfections against Pathogenic Microbes.

Immediately post-production, commercially available bioshell calcium oxide (BiSCaO) water is colorless, transparent, and strongly alkaline (pH 12.8), and is known to possess deodorizing properties and broad microbicidal activity. However, BiSCaO Water may represent a serious safety risk to the living body, given the strong alkalinity. This study aimed to investigate the safety of BiSCaO Water for use as an antiseptic/disinfectant despite concerns regarding its high alkalinity. The change over time in pH of BiSCaO Water was measured during air contact (stirring BiSCaO Water in ambient air). When sprayed on metal, plastic, wood piece, paper, and skin surfaces, the pH of BiSCaO Water decreased rapidly, providing a white powder coating upon drying. Scanning electron microscopy images, energy dispersive X-ray elemental mapping, and X-ray diffractograms showed that the dried powder residues of BiSCaO Water were composed primarily of calcium carbonate. These results suggested that BiSCaO Water is a potent reagent that may overcome the obstacles of being strongly alkaline, making this material appropriate for use in disinfection against pathogenic microbes.

Systematic chemical screening identifies disulfiram as a repurposed drug that enhances sensitivity to cisplatin in bladder cancer: a summary of preclinical studies.

BACKGROUND: Since the standard gemcitabine and cisplatin (GC) chemotherapy for advanced bladder cancer yields limited therapeutic effect due to chemoresistance, it is a clinical challenge to enhance sensitivity to GC. METHODS: We performed high-throughput screening by using a library of known chemicals and repositionable drugs. A total of 2098 compounds were administered alone or with GC to human bladder cancer cells, and chemicals that enhanced GC effects were screened. RESULTS: Disulfiram (DSF), an anti-alcoholism drug, was identified as a candidate showing synergistic effects with cisplatin but not with gemcitabine in multiple cell lines. Co-administration of DSF with GC affected cellular localisation of a cisplatin efflux transporter ATP7A, increased DNA-platinum adducts and promoted apoptosis. Micellar DSF nanoparticles (DSF-NP) that stabilised DSF in vivo, enhanced the inhibitory effect of cisplatin in patient-derived and cell-based xenograft models without severe adverse effects. A drug susceptibility evaluation system by using cancer tissue-originated spheroid culture showed promise in identifying cases who would benefit from DSF with cisplatin. CONCLUSIONS: The present study highlighted the advantage of drug repurposing to enhance the efficacy of anticancer chemotherapy. Repurposing of DSF to a chemotherapy sensitiser may provide additional efficacy with less expense by using an available drug with a well-characterised safety profile.

Preparation and Application of Bioshell Calcium Oxide (BiSCaO) Nanoparticle-Dispersions with Bactericidal Activity.

Scallop-shell powder (SSP) heated at high temperature exhibits high pH and broad antimicrobial activity. Bioshell calcium oxide (BiSCaO) is an SSP composed mainly of calcium oxide. It is poorly water-soluble under alkaline conditions and the generated precipitate can plug spray nozzles. The aim of this study was to establish that BiSCaO dispersion caused no significant CaO loss and plugging of spray nozzles, and to evaluate its deodorization and microbicidal abilities and its ability to reduce the concentrations of NO2- and NO3-. BiSCaO dispersions were prepared by mixing various concentrations of BiSCaO suspension, while phosphate compounds such as Na3PO4, Na2HPO4 or NaH2PO4 and the pH, average diameter, zeta potential, and form of the compounds with cryo-SEM were evaluated. We evaluated deodorization using tainted pork meat and microbicidal efficacy using contaminated suspension with normal bacterial flora. The concentration of NO2- and NO3- after mixing BiSCaO dispersion and pure water containing a high proportion of NO2- and NO3- were measured. BiSCaO dispersion formed with Na2HPO4, whose ratio to BiSCaO was 60%, showed a high pH (>12), a small particle diameter (>181 nm) and was stable for seven days. The BiSCaO dispersion showed higher deodorization and microbicidal activities than SSP-Ca(OH)2, which was mainly composed of Ca(OH)2. BiSCaO, but not SSP-Ca(OH)2, could reduce the concentration of NO2- and NO3- by more than 90% within 15 min. We developed a stable BiSCaO dispersion, and it had high deodorization and microbicidal efficacy. These activities of BiSCaO might result from the high pH caused by CaO hydration and a reduction activity causing active radical species.

Heparinoid Complex-Based Heparin-Binding Cytokines and Cell Delivery Carriers.

Heparinoid is the generic term that is used for heparin, heparan sulfate (HS), and heparin-like molecules of animal or plant origin and synthetic derivatives of sulfated polysaccharides. Various biological activities of heparin/HS are attributed to their specific interaction and regulation with various heparin-binding cytokines, antithrombin (AT), and extracellular matrix (ECM) biomolecules. Specific domains with distinct saccharide sequences in heparin/HS mediate these interactions are mediated and require different highly sulfated saccharide sequences with different combinations of sulfated groups. Multivalent and cluster effects of the specific sulfated sequences in heparinoids are also important factors that control their interactions and biological activities. This review provides an overview of heparinoid-based biomaterials that offer novel means of engineering of various heparin-binding cytokine-delivery systems for biomedical applications and it focuses on our original studies on non-anticoagulant heparin-carrying polystyrene (NAC-HCPS) and polyelectrolyte complex-nano/microparticles (N/MPs), in addition to heparin-coating devices.

[A Case of Partial Prostatectomy for Advanced Rectal Cancer Involving the Prostate in the Jack-Knife Position].

A 72-year-old man was diagnosed with advanced rectal cancer possibly involving the prostate on magnetic resonance imaging (MRI) findings. Following neoadjuvant chemoradiotherapy (CRT), he underwent curative surgery. Confirming negative surgical margin through intraoperative pathological evaluation, colorectectomy with partial prostatectomy was performed in the jack-knife position. No evidence of local recurrence of the tumor was observed one year after surgery without symptoms of the urinary tract. Partial prostatectomy is a choice to be taken into account in the treatment of advanced rectal cancer achieving both the good surgical outcome and the patient's quality of life (QOL).

[Adenocarcinoma of an augmented bladder 49 years after enterocystoplasty : a case report].

A 69-year-old man visited our hospital presenting with bladder tamponade. The patient had undergone bladder augmentation using the ileocecum and the ascending colon for an atrophy bladder due to tuberculosis 49 years previously. Cystoscopy revealed an invasive bladder tumor in the anastomotic region of the bladder and the intestine. He underwent cystourethrectomy and ileal conduit (utilizing the previous ureteroileal anastomosis). A deliberate procedure of urinary tract diversion was required because of the severe postoperative adhesion by the augmentation. The pathological diagnosis showed adenocarcinoma. The tumor spread over the intestinal tract side and the deepest part reached the adventitia of the intestinal tract. The patient is receiving additional therapy of combined modality including chemotherapy.