Therapeutic efficacy and safety of biweekly administration of enfortumab vedotin for urothelial carcinoma.

OBJECTIVES: Enfortumab vedotin (EV) is an established pharmacotherapy for metastatic urothelial carcinoma (mUC); however, its adverse events (AEs) cannot be overlooked. The study investigated the efficacy and safety of biweekly EV administration. METHODS: Patients with mUC who received EV at our institution were included in the study. Eligible patients were classified into two groups as follows: those who received EV on a standard schedule (standard group) and those who received EV on a biweekly schedule (biweekly group); the treatment outcomes and AEs between the two groups were compared. RESULTS: Nine and 19 patients were in the standard group and biweekly groups, respectively. The progression-free survival, overall survival, and overall response rate were not significantly different between the two groups. AEs following EV administration, such as decreased appetite (P < .01), pruritus (P < .01), rash maculopapular (P < .01), anemia (P = .04), and liver dysfunction (P = .04), were significantly more frequent in the standard group. Grade 3 or higher AEs, such as pruritus (P = .03) and rash maculopapular (P < .01), were significantly more frequent in the standard group. Furthermore, significantly more patients in the standard group had to be given a reduced dose due to adverse events (P = .02). CONCLUSIONS: Biweekly administration of EV may be safer without compromising therapeutic efficacy than the standard schedule.

Comprehensive analysis of perioperative hypotension in photodynamic diagnosis-assisted transurethral resection of bladder tumor with 5-aminolevulinic acid.

OBJECTIVE: Intraoperative hypotension remains a serious adverse event of photodynamic diagnosis-assisted transurethral resection of bladder tumor with oral administration of 5-aminolevulinic acid. We conducted a re-analysis of perioperative hypotension in photodynamic diagnosis-assisted transurethral resection of the bladder tumor with oral 5-aminolevulinic acid to ascertain its safety. METHODS: A total of 407 cases who underwent transurethral resection of bladder tumors in our institution were reviewed (274 cases for the PDD group with photodynamic diagnosis and 133 for the white light (WL) group without). A classification of hypotension severity was devised to identify risk factors for clinically troublesome hypotension. The distribution of hypotension severity in each of the PDD and WL groups was compared. Additionally, the patient background and perioperative data by hypotension severity were compared only in the PDD group. RESULTS: More patients with moderate and severe hypotension were noted in the PDD group. The renal function was lower with increasing hypotension severity in the PDD group. More patients on general anesthesia were included in the mild and moderate hypotension group, whereas more patients on spinal anesthesia were included in the severe hypotension group. Furthermore, the frequency of side effects other than hypotension tended to increase with hypotension severity. CONCLUSIONS: Renal function impairment and the other adverse effects of 5-aminolevulinic acid may be risk factors for severe hypotension. Mild or moderate hypotension may be caused by general anesthesia and severe hypotension may be caused by spinal anesthesia. To elucidate specific risk factors, further case-control studies are warranted.

Suppression of androgen receptor signaling induces prostate cancer migration via activation of the CCL20-CCR6 axis.

The suppression of androgen receptor (AR) expression exacerbates the migration potential of prostate cancer. This study identified a previously unrecognized regulation of the AR-controlled pathway that promotes migration potential in prostate cancer cells. Prostate cancer cells that pass through a transwell membrane (mig cells) have a higher migration potential with a decreased AR expression than parental cells. In this study, we aimed to elucidate the mechanism of migration enhancement associated with the suppression of AR signaling. Expression of C-C motif ligand 20 (CCL20) is upregulated in mig cells, unlike in the parental cells. Knockdown of AR with small interfering RNA (siAR) in LNCaP and C4-2B cells increased CCL20 secretion and enhanced the migration of cancer cells. Mig cells, CCL20-treated cells, and siAR cells promoted cell migration with an enhancement of AKT phosphorylation and Snail expression, while the addition of a C-C chemokine receptor 6 (CCR6, the specific receptor of CCL20) inhibitor, anti-CCL20 antibody, and AKT inhibitor suppressed the activation of AKT and Snail. With 59 samples of prostate cancer tissue, CCL20 secretion was profuse in metastatic cases despite low AR expression levels. Snail expression was associated with the expression of CCL20 and CCR6. A xenograft study showed that the anti-CCL20 antibody significantly inhibited Snail expression, thereby suggesting a new therapeutic approach for castration-resistant prostate cancer with the inhibition of the axis between CCL20 and CCR6.

Usefulness of serum CCL2 as prognostic biomarker in prostate cancer: a long-term follow-up study.

OBJECTIVE: Prostate-specific antigen is considered the most useful biomarker for prostate cancer, but not in all cases. In a previous study, we have shown that a risk classification combining prostate-specific antigen ≥100 ng/mL and chemokine (CC motif) ligand 2 ≥ 320 pg/mL can predict survivals. We investigated the long-term usefulness of serum chemokine (CC motif) ligand 2 as a complementary biomarker to prostate-specific antigen and developed a novel risk classification system. METHODS: Serum samples were collected from 379 patients who underwent prostate biopsy at Kanazawa University Hospital between 2007 and 2013, and 255 patients with histologically diagnosed prostate cancer were included in this study. We retrospectively examined the efficacy of serum chemokine (CC motif) ligand 2 as a prognostic biomarker. RESULTS: Patients with chemokine (CC motif) ligand 2 ≥ 320 pg/mL exhibited a significantly shorter overall survival, prostate cancer-specific survival and castration-resistant prostate cancer-free survival than those with chemokine (CC motif) ligand 2 < 320 pg/mL. Multivariate analysis was performed to determine whether chemokine (CC motif) ligand 2 was a useful prognostic factor. Independent significant predictors of worse overall survival were prostate-specific antigen ≥ 100 ng/mL, Gleason score ≥ 8 and chemokine (CC motif) ligand 2 ≥ 320 pg/dL. Prognostic predictors of prostate cancer-specific survival or cancer-free survival in multivariate analysis were prostate-specific antigen ≥ 100 ng/mL and Gleason score ≥ 8. A novel risk classification system was created to predict overall survival in patients based on the number of risk factors present (chemokine (CC motif) ligand 2 ≥ 320 pg/mL, prostate-specific antigen ≥ 100 ng/mL, Gleason score ≥ 8). Scores 2 or 3, 1 and 0 indicated Poor, Intermediate and Good risk groups, respectively. CONCLUSIONS: This study demonstrated the utility of serum chemokine (CC motif) ligand 2 level as a predictive biomarker of long-term overall survival in prostate cancer. A novel risk classification system that predicts long-term overall survival based on the combined indications of chemokine (CC motif) ligand 2 level, prostate-specific antigen level and Gleason score may be a useful prognostic tool for prostate cancer.

Androgen receptor signaling-targeted therapy and taxane chemotherapy induce visceral metastasis in castration-resistant prostate cancer.

BACKGROUND: Visceral metastasis (VM), an important poor prognostic factor of prostate cancer (PC), is not commonly observed in castration sensitive status but is often observed after castration-resistant progression. However, the site, timing of emergence, and incidence of VM in castration-resistant patients have not yet been fully elucidated. METHODS: Demographic, surgical, pathological, and follow-up data of PC patients treated at Kanazawa University Hospital between January 2000 and December 2016 were retrospectively analyzed using their medical charts. From this data, risk factors of VM and survival of patients with VM were elucidated. RESULTS: Of 1364 patients, 21 (1.5%) had VM at diagnosis. Of 179 (13.1%) castration-resistant patients, 55 experienced emergence of new VM during treatment course. Incidence of new VM, especially nonlung, such as liver and adrenal metastases, increased significantly in proportion with the number of prescribed treatments. Multivariate analysis revealed that T stage, M stage, age, and treatment history with androgen receptor (AR) signaling-targeted agents and/or taxanes significantly increased the risk of VM. Compared with the group with VM at diagnosis, survival after diagnosis of VM following treatment was significantly shorter. CONCLUSION: Although sequential use of new AR signaling-targeted agents and taxanes for castration-resistant PC (CRPC) is a standard treatment strategy, it often results in development of VM. Elucidating the mechanisms of VM are essential to improve survival in patients with CRPC.

A new flavonoid derivative exerts antitumor effects against androgen-sensitive to cabazitaxel-resistant prostate cancer cells.

BACKGROUND: Our previous report has shown that the flavonoid 2'-hydroxyflavanone (2'-HF) showed inhibition of androgen receptor (AR) activity against androgen-sensitive prostate cancer (PCa) cells, LNCaP, and exhibited antitumor effects against androgen-insensitive PCa cells, PC-3, and DU145. In the present study, we prepared a derivative of 2'-HF, 16MS7F1924, and confirmed the effects of this derivative on PCa cells. METHODS: The antiproliferation effects of 16MS7F1924 were investigated in PCa cells using LNCaP, PC-3, DU145 and docetaxel-resistant and cabazitaxel-resistant cell lines of PC-3-TxR/CxR and DU145-TxR/CxR. Prostate-specific antigen (PSA) and AR expression level in whole cells and the nucleus were confirmed in LNCaP by reverse transcriptase polymerase chain reaction and Western blot analysis. AR activity in LNCaP cells was confirmed by luciferase assay using PSA promoter-driven reporter. To analyze the antiproliferative effects, cell-based assays using flow cytometry, immunocytochemistry, and TUNEL assay as well as Western blot analysis were employed. Furthermore, PC-3, DU145 and each chemoresistant strain of human PCa cells were subcutaneously xenografted. The antitumor effects of 16MS7F1924 were evaluated in vivo. RESULTS: 16MS7F1924 showed antitumor effect on all PCa cells in a dose-dependent manner. 16MS7F1924 reduced the expression of PSA messenger RNA (mRNA) and protein and inhibited AR activity in a dose-dependent manner, while expression of AR protein and mRNA was reduced by 16MS7F1924. 16MS7F1924 induced mitotic catastrophe and apoptosis. Apoptotic cells were increased in a dose-dependent manner, and the apoptosis was mediated through the Akt pathway. Tumor growth was safely and significantly inhibited by both intraperitoneal and oral administration of 16MS7F1924 in vivo. CONCLUSION: 16MS7F1924 had sufficient antitumor activity against androgen-sensitive and cabazitaxel-resistant PCa cells and may be useful as a novel therapeutic agent overcoming hormone- and chemoresistant PCas.

Effect of ingesting yogurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 on influenza virus-bound salivary IgA in elderly residents of nursing homes: a randomized controlled trial.

Objective: The purpose of this study was to clarify the influence of consuming yogurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 (1073R-1-yogurt) on influenza virus-bound salivary immunoglobulin A (IgA) levels, in the elderly residents of nursing homes. Methods: A double-blind, parallel-group, randomized controlled trial was conducted with 96 elderly volunteers residing in 2 nursing homes. During the trial, participants consumed 100 g of 1073R-1-yogurt every morning for 12 weeks, whereas the control participants consumed yogurt fermented with a different Lactobacillus strain (control yogurt). Saliva was collected before the trial and after 4, 8 and 12 weeks of yogurt ingestion. Results: Our data indicated that consumption of 1073R-1-yogurt affected influenza A virus subtype H3N2-bound IgA levels in saliva (p = .001). In addition, saliva flow rate and total IgA levels increased in response to the yogurt intake period in both the 1073R-1 and control yogurt groups (p = .04). Conclusions: Our study suggests that continuous daily ingestion of 1073R-1-yogurt may help prevent infection with influenza A virus subtype H3N2 in elderly subjects with weakened immunity, by increasing the production of influenza A virus subtype of H3N2-bound salivary IgA.

Hypouricaemic effects of yoghurt containing Lactobacillus gasseri PA-3 in patients with hyperuricaemia and/or gout: A randomised, double-blind, placebo-controlled study.

PURPOSE: Lactobacillus gasseri PA-3 (PA-3) has been previously shown to decrease serum uric acid (SUA) levels in subjects with increased SUA. In this study, we investigated whether PA-3 is also capable of decreasing SUA levels in patients with hyperuricaemia and/or gout. METHODS: Twenty-five patients with hyperuricaemia and/or gout completed this study. Urate-lowering drugs were discontinued for 12 weeks (week -4 to week 8). After flushing of urate-lowering drugs for 4 weeks (week 0), patients were randomised equally to receive diets containing yoghurt beverages with PA-3 or without PA-3 for a duration of 8 weeks (week 8). The intention to treat (ITT) population included all subjects who were randomised, and the per-protocol (PP) population included subjects who completed the experiment with compliance. We evaluated SUA levels at the end of the study as well as changes in SUA levels in comparison to week 0. RESULTS: In both ITT and PP analyses, there were no significant differences in SUA levels or in the changes in SUA levels compared to week 0 between the two groups. However, in a sub-population whose SUA levels at week 0 were within one SD of the mean of the whole PP population, changes in SUA levels in the group consuming PA-3-containing yoghurt were significantly lower than those of the control group (p = .0378). CONCLUSION: PA-3-containing yoghurt improves SUA levels, even in patients with hyperuricaemia and/or gout.

Immunoregulatory effects triggered by immunobiotic Lactobacillus jensenii TL2937 strain involve efficient phagocytosis in porcine antigen presenting cells.

BACKGROUND: Immunobiotic Lactobacillus jensenii TL2937 modulates porcine mononuclear phagocytes from Peyer's patches (PPMPs) and induces a differential production of pro- and anti-inflammatory cytokines in response to Toll-like receptor (TLR)-4 activation. In view of the important role played by phagocytosis in the activation of antigen presenting cells (APCs), the aim of the present work was to examine the interaction of TL2937 with porcine PPMPs focusing on phagocytosis. In addition, this study aimed to investigate whether the effects of L. jensenii TL2937 in porcine blood monocyte-derived dendritic cells (MoDCs) are similar to those found in PPMPs considering that MoDCs do not recapitulate all functions of mucosal APCs. RESULTS: Studies showed a high ability of porcine CD172a(+) PPMPs to phagocytose L. jensenii TL2937. Interestingly, our results also revealed a reduced capacity of the non-immunomodulatory L. plantarum TL2766 to be phagocytosed by those immune cells. Phagocytosis of L. jensenii TL2937 by porcine PPMPs was partially dependent on TLR2. In addition, we demonstrated that TL2937 strain was able to improve the expression of IL-1ß, IL-12 and IL-10 in immature MoDCs resembling the effect of this immunobiotic bacterium on PPMPs. Moreover, similarly to PPMPs those immunomodulatory effects were related to the higher capacity of TL2937 to be phagocytosed by immature MoDCs. CONCLUSIONS: Microbial recognition in APCs could be effectively mediated through ligand-receptor interactions that then mediate phagocytosis and signaling. For the immunobiotic strain TL2937, TLR2 has a partial role for its interaction with porcine APCs and it is necessary to investigate the role of other receptors. A challenge for future research will be advance in the full understanding of the molecular interactions of immunobiotic L. jensenii TL2937 with porcine APCs that will be crucial for the successful development of functional feeds for the porcine host. This study is a step in that direction.

Enhanced natural killer cell activation by exopolysaccharides derived from yogurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1.

Yogurt is generally recognized as a beneficial food for our health, but research into its physiological effects has focused mainly on intestinal dysfunctions such as constipation and diarrhea. We previously found yogurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 (hereafter OLL1073R-1) could reduce risks of catching the common cold and flu in human trials. It was assumed that immunostimulatory exopolysaccharide (EPS) produced from OLL1073R-1 play an important role in this context. However, few studies have examined the immunostimulatory effects of traditional Bulgarian yogurts fermented with different strains of lactobacilli and their metabolites. Therefore, we screened 139 L. delbrueckii ssp. bulgaricus strains and identified OLL1073R-1 as the most robust producer of EPS. This strain was also the only strain that induced the production of IFN-γ in vitro. Oral administration of the EPS or yogurt fermented with OLL1073R-1 and Streptococcus thermophilus OLS3059 (OLL1073R-1 yogurt) augmented natural killer (NK) cell activity and induced IFN-γ production in spleen cells in mice, whereas 2 other yogurts fermented with other strains had no effect on NK cell activity. Cellular preparations of the OLL1073R-1 strain also slightly augmented NK cell activity, but were less effective than EPS itself. The EPS-dependent stimulation of NK cell activity was abrogated in IFN-γ knockout mice and in myeloid differentiation factor 88 knockout mice. Furthermore, IFN-γ production from spleen cells stimulated with EPS was completely blocked with both anti-IL-12 and anti-IL-18 antibodies in vitro. These findings suggest that NK cell activation by OLL1073R-1 yogurt is EPS-dependent, occurs via IL-12- and IL-18-mediated IFN-γ production, and requires myeloid differentiation factor 88. We showed that traditional Bulgarian yogurt could exert immunostimulatory effects by selecting starter strains and part of the mechanisms depend on IFN-γ inducible EPS produced from L. delbrueckii ssp. bulgaricus. Further investigations on processes of fermentation to increase of the EPS may lead to the development of new functional foods that keep our immune functions stable.

Does the quality of endoscopic equipment influence the recurrence rate after photodynamic diagnosis-assisted transurethral resection of bladder tumor?

BACKGROUND: Photodynamic diagnosis-assisted transurethral resection of bladder tumor (PDD-TURBT) for nonmuscle-invasive bladder cancer is superior to conventional white-light TURBT for cancer detection. However, when performing PDD-TURBT, cystoscopy findings vary depending on the quality of the endoscopic equipment. In this study, we compared the effects of different types of endoscopic equipment on postoperative outcomes. METHODS: Patients who underwent their first PDD-TURBT at our clinic were selected. Patients on whom PDD-TURBT was performed using endoscopic equipment A were sorted into Group A, and patients on whom PDD-TURBT was performed using equipment S were sorted into Group S. The characteristics, recurrence-free survival (RFS), and recurrence frequency of these patients were retrospectively investigated and compared. The prognostic factors for RFS were also analyzed. RESULTS: A total of 49 patients were included in Group A and 46 in Group S. In Group S, a higher detection rate (8.2% vs. 30.4 %, p < 0.01) of carcinoma in situ (CIS) was noted. RFS tended to be better in Group S (HR 0.63, p = 0.15). The frequency of recurrence also tended to be lower in Group S (4.92 vs. 3.66 per 10,000 person-days, p = 0.08). Furthermore, CIS (HR 0.30, p = 0.04) and Bacillus Calmette-Guerin therapy (HR: 0.26, p = 0.01) were significant favorable prognostic factors for RFS. CONCLUSION: The quality of the endoscopic equipment may influence postoperative recurrence after PDD-TURBT. Higher-quality endoscopic instruments have superior CIS detection capabilities, which can lead to improvements in postoperative outcomes with the appropriate selection of postoperative adjuvant therapy.

Salvage Androgen Deprivation Therapy as Potential Treatment for Recurrence after Robot-Assisted Radical Prostatectomy.

BACKGROUND: The efficacy of intermittent androgen deprivation therapy (ADT) for biochemical recurrence (BCR) after robot-assisted radical prostatectomy (RARP) is unknown, and its usefulness in Japanese practice needs to be investigated. METHODS: We conducted a retrospective analysis of 85 patients who underwent RARP and were selected for intermittent ADT for postoperative recurrence at Kanazawa University Hospital between 2009 and 2019. Intermittent ADT was administered for 2 years. If prostate-specific antigen levels increased post-treatment, intermittent ADT was reinitiated. The median follow-up period was 47 months. RESULTS: The 73 patients had completed the initial course of ADT, and 12 were under initial ADT. The 5-year castration-resistant prostate-cancer-free survival rates, cancer-specific survival, and overall survival were 92.7%, 98.3%, and 94.7%, respectively. A subgroup analysis of 69 patients who completed intermittent ADT was conducted to evaluate the BCR rate following initial ADT. The 5-year BCR-free survival rate was 53.2%. Multivariate analysis identified testosterone ≤ 0.03 ng/mL during ADT as the sole predictor of BCR after ADT. CONCLUSIONS: Salvage intermittent ADT may be an effective treatment option for BCR after RARP. In addition, it would be useful to confirm strong testosterone suppression as a criterion for transition to intermittent therapy.

Procalcitonin in advanced urological cancer-bacterial versus non-bacterial infections: prospective cohort study.

OBJECTIVES: Patients with advanced cancer may develop bacterial infections (BI) as their general condition worsens, but general blood tests often find it difficult to distinguish them from non-bacterial infections (NBI). The present prospective study was undertaken to investigate the effectiveness of serum procalcitonin levels in distinguishing between BI and NBI in patients with advanced urological cancer. METHODS: This study prospectively evaluated patients diagnosed with locally advanced or metastatic or recurrent urological cancer in our department from September 2013 to December 2019. Body temperature was measured in the axilla and the measurement results were recorded. Febrile episodes of ≥38.0°C were analysed, and written patient consent was obtained at the onset of the fever. RESULTS: Of 75 patients enrolled in the present study, 90 febrile episodes were analysed. A total of 34 of 90 febrile episodes were regarded as BI, and the remaining 56 febrile episodes as NBI. The median procalcitonin value was significantly higher in the BI group (p=0.0015), while no significant difference was found between the two groups for white blood cell count and C reactive protein. Additionally, a white blood cell count of less than 1.0×10ˆ9/L resulted in BI in all cases. The procalcitonin receiver operating characteristic area under the curve was 0.710 (95% CI 0.586 to 0.83), excluding cases with white blood cell counts of <1.0 × 103/µL. CONCLUSIONS: Procalcitonin is a rapid and affordable marker for differentiation between BI and NBI in patients with advanced urological cancer.

Bone Turnover Markers, n-Terminal Propeptide of Type I Procollagen and Tartrate-Resistant Acid Phosphatase Type 5b, for Predicting Castration Resistance in Prostate Cancer.

Bone is a common site of prostate cancer metastasis. Bone turnover markers n-terminal propeptide of type I procollagen (P1NP) and tartrate-resistant acid phosphatase type 5b (TRACP-5b) are highly sensitive to bone remodeling activity. However, their prognostic significance as markers of prostate cancer is unknown. This study retrospectively examined the usefulness of P1NP and TRACP-5b as prognostic biomarkers. Castration-resistant prostate cancer recurrence-free survival (CFS) was estimated using the Kaplan-Meier method. A predictive model for CFS was constructed using multivariate analysis. This study enrolled 255 patients diagnosed with prostate cancer at Kanazawa University Hospital. The median follow-up was 115.1 months. Patients with both high serum P1NP and TRACP-5b levels, defined as having a poor bone turnover category (BTC), had significantly shorter CFS. Multivariate analysis identified Gleason score, metastasis, and BTC poor as predictors for castration resistance in prostate cancer. Using these three factors, a prognostic model was established, categorizing patients into low-risk (no or one factor) and high-risk (two or three factors) groups. In the low-risk group, the median CFS was not reached, contrasting with 19.1 months in the high-risk group (hazard ratio, 32.23, p < 0.001). Combining P1NP and TRACP-5b may better predict castration resistance.

High-resolution simultaneous microscopy of refractive index and fluorescent intensity distributions by using localized surface plasmons.

We propose a localized surface plasmon microscope that provides simultaneous imaging of refractive index and fluorescent intensity distributions. We show experimental images of fluorescent and transparent particles under circular pupil illumination to confirm simultaneous high-resolution imaging. Furthermore, we investigate applicability of annular pupil illumination employing two axicons to improve energy efficiency in the fluorescent imaging and find that a brighter image is obtainable by maintaining high spatial resolution for both imaging modes.

Oral administration of Lactobacillus delbrueckii subspecies bulgaricus OLL1073R-1 suppresses inflammation by decreasing interleukin-6 responses in a murine model of atopic dermatitis.

The oral intake of Lactobacillus spp. can provide beneficial effects to the host by modulating the immune response. Atopic dermatitis (AD) is an allergic inflammatory disease mediated by various immune responses. In this study, we examined the effect of a Lactobacillus strain, Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 (OLL1073R-1), on AD development in a murine model of AD that was developed by the topical application of mite antigen in NC/Nga mice. The oral intake of heat-killed OLL1073R-1 cells inhibited both the development of dermatitis and the elevation of an acute inflammation marker, serum amyloid A. Another bacterial strain, Lactobacillus rhamnosus OLL2984, exerted no inhibitory effects on dermatitis. The oral intake of heat-killed OLL1073R-1 cells also attenuated secretion of IL-6 from lymph node cells in response to mite antigen and reduced IL-6 levels in inflamed tissues, such as auricles. Production of IFN-γ or IL-4 was not influenced by OLL1073R-1 intake. We also found that inhibition of IL-6 signaling by gp130-Fc (a fusion protein consisting of the extracellular portion of glycoprotein 130 fused to the Fc region of human IgG1) markedly decreased the severity of dermatitis in NC/Nga mice. Moreover, secretion of IL-6 by lymph node cells was augmented in NC/Nga mice compared with that in BALB/c mice. These results indicate that IL-6 plays an essential role in the development of dermatitis in the NC/Nga mouse model of AD, and that OLL1073R-1 inhibits dermatitis, at least in part, by suppressing the IL-6 response.

Heat treatment in the presence of arginine increases the emulsifying properties of soy proteins.

This study aimed to improve the emulsifying properties of commercial soy protein isolates (CSPIs). CSPIs were thermally denatured without additives (CSPI_H) and with arginine (CSPI_A), urea (CSPI_U), and guanidine hydrochloride (CSPI_G), which improve protein solubility to prevent aggregation. These additives were removed by dialysis, and the samples were lyophilized. CSPI_A resulted in high emulsifying properties. FT-IR analysis showed that the ß-sheet content in CSPI_A was reduced compared to that of untreated CSPI (CSPI_F). Fluorescence analysis showed that the tryptophan-derived emission peak of CSPI_A shifted between CSPI_F and CSPI_H which was exposed to hydrophobic amino acid chains with aggregation. As a result, the structure of CSPI_A became moderately unfolded and exposed the hydrophobic amino acid chains without aggregation. The CSPI_A solution had a more reduced oil-water interface tension than other CSPIs. These results support that CSPI_A attaches efficiently to the oil-water interface and produces small, less flocculated emulsions.

Consumption of yogurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 augments serum antibody titers against seasonal influenza vaccine in healthy adults.

Seasonal influenza is a major upper respiratory tract infection occurring in winter. Vaccination is the best method for preventing this infection. We conducted two randomized, double-blind, placebo-controlled trials to examine whether consumption of yogurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1, which has been reported to reduce the risk of catching the common cold, augments serum antibody titers against seasonal influenza vaccines. In the first trial, which included university students, serum antibody titers against influenza A (H3N2) and B viruses were significantly higher in the yogurt group than in the placebo group. According to the guidelines established by the European Medicines Agency (EMA) for the assessment of vaccines, the seroconversion rate and mean geometric increase of influenza A (H3N2) and seroprotection of influenza B met the criteria only in the yogurt group. In the second trial, which included healthy adults, serum antibody titers against influenza A (H1N1) and B viruses were significantly higher in the yogurt group than in the placebo group. The seroconversion rate and mean geometric increase of influenza B met the EMA criteria only in the yogurt group. Furthermore, the cumulative days of ill health, such as throat complaints, upper respiratory inflammation, and cold, were significantly lower in the yogurt group than in the placebo group. Therefore, daily intake of yogurt fermented with L. bulgaricus OLL1073R-1 could reduce the duration of symptoms caused by respiratory infections and act as a mucosal adjuvant enhancing acquired immune responses against vaccines, leading to the improvement of public health.

Role of Positive Biopsy Core Ratio in Prostate Cancer Patients.

BACKGROUND/AIM: The percentage of positive cores (PPC) is increasingly recognized as a prognostic factor in prostate cancer. However, the usefulness of PPC for patients undergoing androgen deprivation therapy (ADT) and high-risk group has not been adequately studied. PATIENTS AND METHODS: A retrospective analysis was conducted of 255 patients who underwent prostate biopsy (all-case group). We examined the efficacy of PPC as a prognostic biomarker. RESULTS: Eighty-nine patients were treated with ADT alone (ADT group), and 107 patients were classified as high-risk (high-risk group). The median duration of follow-up was 112.4 months, 85.3 months, and 110.0 months for the all-case, ADT, and high-risk groups, respectively. Patients with PPC >60% had significantly shorter prostate cancer-specific survival (CSS) and castration-resistant prostate cancer-free survival (CFS) in the all-case and ADT groups. In the high-risk group, patients with PPC >60% had shorter CFS but no difference in CSS. Multivariate analysis showed that significant independent predictors of prostate CSS were the presence of metastasis at diagnosis and PPC >60% in the all-case and ADT groups. CONCLUSION: PPC may be a prognostic factor in ADT treated and high-risk prostate patients.

Novel α-Trifluoromethyl Chalcone Exerts Antitumor Effects Against Prostate Cancer Cells.

BACKGROUND/AIM: Despite treating advanced prostate cancer (PCa) with androgen deprivation therapy, it eventually progresses to castration-resistant PCa. Subsequently, taxanes are administered, but when PCa becomes resistant to taxanes, another treatment is needed, which has not yet been established. We previously synthesized a novel α-trifluoromethyl chalcone, YS71, and reported its antitumor effects against PCa cells. In this study, we confirmed its efficacy against androgen-sensitive, androgen-independent, and taxane-resistant PCa cells. MATERIALS AND METHODS: The PCa cell lines used were LNCaP, PC-3, DU145, PC-3-TxR (paclitaxel-resistant), PC-3-TxR/CxR (paclitaxel- and cabazitaxel-resistant), DU145-TxR, and DU145-TxR/CxR. The antiproliferative effects of YS71 were evaluated using proliferation assay. The reverse transcriptase transcription-polymerase chain reaction and western blot were performed to determine the expression level of androgen receptor (AR), whereas luciferase assay was performed to determine the AR activity. Furthermore, TUNEL assay and western blot were performed to investigate the mechanism of the antiproliferative effect. RESULTS: YS71 exerted a dose-dependent antitumor effect, inhibited AR activity, and induced apoptosis in all PCa cells in a dose-dependent manner. Western blot showed that YS71 increased the levels of apoptosis-related proteins, cleaved caspase-3, and cleaved PARP, and decreased the levels of the antiapoptotic proteins, Bcl-xL and Bcl-2. In addition, microarray analysis revealed that YS71 decreased several cancer-related genes. CONCLUSION: YS71 exhibits antitumor activity by inducing apoptosis in PCa cells, including taxane-resistant cells. It could be a potential future therapeutic option for hormone- and chemotherapy-resistant PCa.