Gas-Phase Biosensors (Bio-Sniffers) for Measurement of 2-Nonenal, the Causative Volatile Molecule of Human Aging-Related Body Odor.

The molecule 2-nonenal is renowned as the origin of unpleasant human aging-related body odor that can potentially indicate age-related metabolic changes. Most 2-nonenal measurements rely on chromatographic analytical systems, which pose challenges in terms of daily usage and the ability to track changes in concentration over time. In this study, we have developed liquid- and gas-phase biosensors (bio-sniffers) with the aim of enabling facile and continuous measurement of trans-2-nonenal vapor. Initially, we compared two types of nicotinamide adenine dinucleotide (phosphate) [NAD(P)]-dependent enzymes that have the catalytic ability of trans-2-nonenal: aldehyde dehydrogenase (ALDH) and enone reductase 1 (ER1). The developed sensor quantified the trans-2-nonanal concentration by measuring fluorescence (excitation: 340 nm, emission: 490 nm) emitted from NAD(P)H that was generated or consumed by ALDH or ER1. The ALDH biosensor reacted to a variety of aldehydes including trans-2-nonenal, whereas the ER1 biosensor showed high selectivity. In contrast, the ALDH bio-sniffer showed quantitative characteristics for trans-2-nonenal vapor at a concentration range of 0.4-7.5 ppm (with a theoretical limit of detection (LOD) and limit of quantification (LOQ) of 0.23 and 0.26 ppm, respectively), including a reported concentration (0.85-4.35 ppm), whereas the ER1 bio-sniffer detected only 0.4 and 0.8 ppm. Based on these findings, headspace gas of skin-wiped alcohol-absorbed cotton collected from study participants in their 20s and 50s was measured by the ALDH bio-sniffer. Consequently, age-related differences in signals were observed, suggesting the potential for measuring trans-2-nonenal vapor.

Granulocyte colony-stimulating factor producing retroperitoneal leiomyosarcoma.

INTRODUCTION: Granulocyte colony-stimulating factor-producing nonhematopoietic malignancies have poor clinical outcomes. CASE PRESENTATION: A 62-year-old woman complaining of fever and left lower quadrant pain was referred to our hospital. A left retroperitoneal tumor was suspected on computed tomography, and laboratory data showed leukocytosis and markedly elevated granulocyte colony-stimulating factor. She underwent left nephroureterectomy, partial colectomy, and psoas muscle resection. The histological examination showed a granulocyte colony-stimulating factor-producing retroperitoneal leiomyosarcoma. Three months after the operation, she developed lung and liver metastases and received the chemotherapy, including doxorubicin and ifosfamide. Eight months after the operation, these lesions had progressed, and a new bone metastasis appeared. Twelve months after the operation, she received pazopanib and radiation for bone metastases. However, the metastases progressed, and she died 17 months after the operation. CONCLUSION: Since granulocyte colony-stimulating factor-producing retroperitoneal leiomyosarcoma had a very poor prognosis irrespective of intensive treatment including wide resection, effective systemic therapy should be required.

Predictive Factors for Prolonged Urination Disorder After Permanent 125I Brachytherapy for Localized Prostate Cancer.

BACKGROUND: We assessed the change in LUTS after prostate brachytherapy to reveal factors for prolonged urination disorder. MATERIALS AND METHODS: Four hundred and four patients received prostate brachytherapy at our institution and were followed-up for at least 2 years. We evaluated the correlation of mean IPSS changes and clinical factors. Using multivariate analysis, we also evaluated clinical factors with potential to delay IPSS resolution. RESULTS: In cases with prostate volume more than 30 cm3, radiation dose to 90% of prostate volume (D90) more than 160 Gy, and radiation dose to 30% of the urethral volume (UD30) more than 240 Gy, mean IPSS levels were significantly higher, even 30 months after treatment. On multivariate analysis, baseline IPSS more than 8 points and D90 more than 160 Gy were significant predictors for delayed IPSS resolution. CONCLUSION: Our data suggest that higher baseline IPSS and higher D90 were predictors for prolonged urination disorder.

The Involvement of Hepatocyte Growth Factor-MET-Matrix Metalloproteinase 1 Signaling in Bladder Cancer Invasiveness and Proliferation. Effect of the MET Inhibitor, Cabozantinib (XL184), on Bladder Cancer Cells.

OBJECTIVE: To clarify the invasive mechanisms of muscle-invasive bladder cancer (BCa) would be useful for the determination of appropriate treatment strategies. We previously showed that hepatocyte growth factor (HGF)-MET signaling is correlated with invasiveness of BCa cells. Here, we investigated the effects of the MET inhibitor, cabozantinib (XL184), on BCa cells. METHODS: We first conducted Western blot analysis to investigate MET expression in BCa cell lines. Next, we examined the effect of cabozantinib on their proliferation and invasive abilities using MTT and Matrigel invasion assays, respectively. Invasion assays were performed using the xCELLigence system. Additionally, to investigate the biological function of HGF-MET signaling, we analyzed gene expression profiles and performed real-time polymerase chain reaction analyses of 5637 cells that were cultivated with or without HGF stimulation, with or without cabozantinib. RESULTS: MET was highly expressed in 4 of 5 BCa cell lines, and 5637 and T24 cells showed especially high protein expression of MET. Cabozantinib suppressed cell proliferation and invasion (cell index; mock, 1.49 vs HGF, 2.26 vs HGF + XL184, 1.47, P < .05). Gene expression profile analysis indicated that matrix metalloproteinase 1 (MMP1) was significantly elevated at the mRNA level with addition of HGF. Moreover, cabozantinib suppressed HGF-induced MMP1 expression in 5637 T24 cells. CONCLUSIONS: These data indicate that cabozantinib suppressed MMP1 expression by blocking HGF-MET signaling and that HGF-MET-MMP1 signaling is involved in the invasiveness and proliferation of BCa cells. These results suggest that cabozantinib might prove useful for future treatment of muscle-invasive BCa.

Galectin-3 Is Implicated in Tumor Progression and Resistance to Anti-androgen Drug Through Regulation of Androgen Receptor Signaling in Prostate Cancer.

BACKGROUND: Castration-resistant prostate cancer (CRPC)-related deaths are increasing worldwide. Therefore, clarification of the mechanisms of hormone-related tumor progression and resistance to anti-androgen drugs is useful in order to develop strategies for appropriate treatment of CRPC. Galectin-3 has been shown to be correlated with tumor progression in a variety of cancer types through the regulation of tumor proliferation, angiogenesis, and apoptosis. MATERIALS AND METHODS: We examined tumor cell invasion and migration using the xCELLigence system. Control LNCaP and galectin-3-expressing LNCaP (LNCaP-Gal-3) cells were cultured with androgen-depleted medium with 5% charcoal-stripped serum. Cells were treated for 24 h with or without dihydrotestosterone alone or combined with MDV3100 and bicalutamide; gene profile was then analyzed by microarray analysis and mRNA expression was confirmed by quantitative real-time polymerase chain reaction (qRT-PCR). We evaluated tumor growth using spheroids and xenograft tumor growth in a mouse model. RESULTS: In vitro, LNCaP-Gal-3 cells promoted both cell migration and invasion in an androgen-independent manner compared to control LNCaP cells. Galectin-3 also enhanced anchorage-independent growth and xenograft tumor growth even after castration. Importantly, galectin-3 greatly enhanced transcriptional activity of the androgen receptor (AR), especially on treatment with dihydrotestosterone. In microarray and qRT-PCR analyses, galectin-3 increased the expression of several AR-target genes, such as kallikrein-related peptidase 3 (KLK3), and transmembrane protease, serine 2 (TMPRSS2). These AR-target genes were not fully suppressed by anti-androgen drugs such as bicalutamide or MDV3100. Galectin-3 significantly inhibited the effect induced by anti-androgen drugs MDV3100 and bicalutamide, suggesting that galectin-3 may be involved in resistance to anti-androgen drug through enhancement of transcriptional activity of AR and expression of AR-related genes. CONCLUSION: These results suggest that galectin-3 is a potential target molecule for future treatment of anti-androgen drug-resistant prostate cancer.

Clinical Significance of Neoadjuvant Combined Androgen Blockade for More Than Six Months in Patients with Localized Prostate Cancer Treated with Prostate Brachytherapy.

INTRODUCTION: The aim of this study is to clarify the clinical significance of neoadjuvant combined androgen blockade (CAB) for ≥ 6 months in patients with localized prostate cancer. PATIENTS AND METHODS: A total of 431 patients with localized prostate cancer who underwent prostate brachytherapy (BT) with or without neoadjuvant CAB for ≥ 6 months with mean follow-up time of 64.6 months (range 24-108 months) were evaluated retrospectively. Of those 431, 232 patients received BT in combination with neoadjuvant CAB for ≥ 6 months. Biochemical recurrence-free rates (BRFRs) in 364 patients with at least 3 years of follow-up were evaluated by log-rank test. RESULTS: BRFR in patients with low-, intermediate- and high-risk prostate cancer were 98.1, 94.2 and 89.1%, respectively. In patients with intermediate-risk prostate cancer only, neoadjuvant CAB was significantly associated with BRFR (p = 0.0468). Especially in patients with intermediate-risk prostate cancer with radiation dose received by 90% of the prostate (D90) < 180 Gy, neoadjuvant CAB exerted a favorable impact on BRFR (p = 0.0429). On multivariate analyses, neoadjuvant CAB and D90 were independent predictors of BRFR (p = 0.0061 and p < 0.0001, respectively). CONCLUSIONS: Neoadjuvant CAB for ≥ 6 months has a favorable impact on BRFR in patients with intermediate-risk prostate cancer, particularly in patients with relatively low radiation doses of D90.

Complications of Flexible Ureteroscopic Treatment for Renal and Ureteral Calculi during the Learning Curve.

BACKGROUND: The flexible ureterorenoscope (URS) and associated devices have developed rapidly. However, despite its therapeutic benefits, URS may be associated with some complications. To the best of our knowledge, there are no studies discussing the complications of flexURS during the learning curve. METHODS: A retrospective review of the records of patients who underwent flexURS from January 2005 to June 2013 was performed. To compare the complications after the introduction of flexURS, patients were divided into four groups based on the surgeon's training experience, that is, based on the number of cases performed by the surgeon. A total of 219 cases underwent flexURS. Groups 1, 2, 3, and 4 included 35, 50, 50, and 84 cases, respectively. The complications were classified using the Clavien system (I-IV). RESULTS: The mean operation time and stone-free rate were significantly different (p < 0.001, p = 0.013, respectively). The total complication rates were 13.6, 10, 8.3, and 3.2%, respectively (p = 0.068). The more the surgeon's experience, the less was the complication rate. Despite our best efforts, the incidence of urosepsis was not reduced (p = 0.902). CONCLUSIONS: To reduce severe complications, it is necessary to have performed about 100 cases. Increased surgeon experience tended to decrease the risk of severe complications, but the incidence of urosepsis was not reduced.