Role of Signaling Transduction Pathways in Development of Castration-Resistant Prostate Cancer

Almost all patients who succumb to prostate cancer die of metastatic castration-resistant disease. Although docetaxel is the standard treatment for this disease and is associated with modest prolongation of survival, there is an urgent need for novel treatments for castration-resistant prostate cancer (CRPC). Great advances in our understanding of the biological and molecular mechanisms of prostate cancer progression have resulted in many clinical trials of numerous targeted therapies. In this paper, we review mechanisms of CRPC development, with particular focus on recent advances in the understanding of specific intracellular signaling pathways participating in the proliferation of CRPC cells

尿道原発と考えられた悪性リンパ腫の1例

82歳女.主訴は排尿困難と残尿感.膀胱底部から尿道周囲にかけて鶏卵大の腫瘤を認め, 生検で非ホジキンリンパ腫と診断された.他臓器に病変を認めなかった為, 尿道原発の悪性リンパ腫と診断し放射線療法を施行した.治療後, 腫瘍は著明に縮小したが肺転移が出現した.エトポシド単剤による化学療法を追加したが, 放射線治療後5ヵ月で腫瘍の急激な増加を認め癌死したA patient with a primary malignant lymphoma surrounding the female urethra is reported. Despite the good response of the primary tumor to radiotherapy, the patient died shortly after diagnosis due to disseminated disease. We reviewed 16 cases of this rare entity reported previously

Gliding Basal Cell Migration of the Urothelium during Wound Healing

Collective cell migration during wound healing has been extensively studied in the epidermis. However, it remains unknown whether the urothelium repairs wounds in a manner similar to the epidermis. By in vivo two-photon excitation microscopy of transgenic mice that express fluorescent biosensors, we studied the collective cell migration of the urothelium in comparison with that of the epidermis. In vivo time-lapse imaging revealed that, even in the absence of a wound, urothelial cells continuously moved and sometimes glided as a sheet over the underlying lamina propria. On abrasion of the epithelium, the migration speed of each epidermal cell was inversely correlated with the distance to the wound edge. Repetitive activation waves of extracellular signal–regulated kinase (ERK) were generated at and propagated away from the wound edge. In contrast, urothelial cells glided as a sheet over the lamina propria without any ERK activation waves. Accordingly, the mitogen-activated protein kinase/ERK kinase inhibitor PD0325901 decreased the migration velocity of the epidermis but not the urothelium. Interestingly, the tyrosine kinase inhibitor dasatinib inhibited migration of the urothelium as well as the epidermis, suggesting that the gliding migration of the urothelium is an active, not a passive, migration. In conclusion, the urothelium glides over the lamina propria to fill wounds in an ERK-independent manner, whereas the epidermis crawls to cover wounds in an ERK-dependent manner

Attenuation of Immune-Mediated Renal Injury by Telmisartan, an Angiotensin Receptor Blocker and a Selective PPAR-γ Activator

Background/Aims: Anti-glomerular basement membrane (GBM) nephritis is characterized by activation of the renin-angiotensin system. This study aimed to determine the question of whether a temporary angiotensin II blockade at the initial stage of anti-GBM nephritis is able to attenuate the disease as well as differences in renoprotection among angiotensin II receptor blockers (ARBs) with distinct peroxisome proliferator-activated receptor (PPAR)-γ-modulating activities. Methods: C57BL/6J mice were immunized with rabbit IgG, followed by intravenous injection of rabbit anti-mouse antibodies. Mice were then treated with telmisartan, losartan, and telmisartan + GW9662 (a PPAR-γ antagonist) for 5 days, or hydralazine for 9 days. On days 8 and 13, mice were sacrificed to obtain tissues for histological analysis. Results: The temporary administration of telmisartan significantly suppressed glomerular damage compared to hydralazine. Losartan showed a similar effect but was less effective. Co-administration of GW9662 attenuated the renoprotective effect of telmisartan, almost to levels observed with losartan. In particular, it limited the decreased infiltration of inflammatory cells and preservation of capillaries in the glomeruli induced by telmisartan. Conclusion: Temporary angiotensin II blockade at the initial stage of anti-GBM disease dramatically inhibited its progression. In addition to a class effect of ARBs, telmisartan modified inflammation and endothelial damage in the kidney through its PPAR-γ-agonistic action

Gosha-jinki-gan Reduces Transmitter Proteins and Sensory Receptors Associated with C Fiber Activation Induced by Acetic Acid in Rat Urinary Bladder

This is a preprint of an article published in [NEUROUROLOGY AND URODYNAMICS. 27(8):832-837 (2008)].ArticleNEUROUROLOGY AND URODYNAMICS. 27(8):832-837 (2008)journal articl

Pathways Involving Beta-3 Adrenergic Receptors Modulate Cold Stress-Induced Detrusor Overactivity in Conscious Rats

ObjectiveTo investigate pathways involving beta-3 adrenergic receptors (ARs) in detrusor overactivity induced by cold stress, we determined if the beta-3 AR agonist CL316243 could modulate the cold stress-induced detrusor overactivity in normal rats. MethodsTwodays prior to cystometric investigations, the bladders of 10-week-old female Sprague-Dawley rats were cannulated. Cystometric measurements of the unanesthetized, unrestricted rats were taken to estimate baseline values at room temperature (RT, 272 degrees C) for 20min. They were then intravenously administered vehicle, 0.1, or 1.0mg/kg CL316243 (n=6 in each group). Fiveminutes after the treatments, they were gently and quickly transferred to the low temperature (LT, 42 degrees C) room for 40min where the cystometric measurements were again made. Afterward, the rats were returned to RT for final cystometric measurements. The cystometric effects of CL316243 were also measured at RT (n=6 in each group). ResultsAt RT, both low and high dose of CL316243 decreased basal and micturition pressure while the high dose (1.0mg/kg) significantly increased voiding interval and bladder capacity. During LT exposure, the high dose of CL316243 partially reduced cold stress-induced detrusor overactivity characterized by increased basal pressure and urinary frequency. The high drug dose also significantly inhibited the decreases of both voiding interval and bladder capacity compared to the vehicle- and low dose (0.1mg/kg)-treated rats. ConclusionA high dose of the beta-3 agonist CL316243 could modulate cold stress-induced detrusor overactivity. Therefore, one of the mechanisms in cold stress-induced detrusor overactivity includes a pathway involving beta-3 ARs.ArticleLUTS-LOWER URINARY TRACT SYMPTOMS.7(1):50-55(2014)journal articl

Brachial-ankle pulse wave velocity and symptomatic cerebral infarction in patients with type 2 diabetes: a cross-sectional study

BACKGROUND: Recently a new automatic device that measures brachial-ankle pulse wave velocity using an oscillometric method has been developed. However, the practical significance of brachial-ankle pulse wave velocity measurement remains uncertain. The purpose of this study was to examine the association between brachial-ankle pulse wave velocity and symptomatic cerebral infarction in patients with type 2 diabetes. METHODS: One thousand sixty six patients with type 2 diabetes were studied cross-sectionally. Measurements of brachial-ankle pulse wave velocity were made using the automatic device. Logistic regression analysis was used to calculate the odds ratio for cerebral infarction. RESULTS: The presence of symptomatic cerebral infarction was confirmed in 86 patients. In these patients brachial-ankle pulse wave velocity was found to be significantly higher than in patients without cerebral infarction (18.94 ± 4.95 versus 16.46 ± 3.62 m/s, p < 0.01). The association between brachial-ankle pulse wave velocity and cerebral infarction remained significant after adjustment for traditional risk factors. There was an increasing odds ratio for each tertile of brachial-ankle pulse wave velocity, from the second tertile (odds ratio, 2.28; 95% confidence interval, 1.05 to 4.94), to the third (odds ratio, 2.53; 95% confidence interval, 1.09 to 5.86). CONCLUSION: Overall, we conclude that an increase in brachial-ankle pulse wave velocity is associated with symptomatic cerebral infarction in patients with type 2 diabetes

Lattice Parameter of Titanium Monoxides under High Pressure

The effect of pressure on the crystal structure and the lattice parameter of vacancy rich titanium monoxides has been studied using a high pressure apparatus of the tetrahedral anvil type combined with an X-ray diffraction equipment. Two kinds of specimens, TiO_ and TiO_, have been used, the former containing most of vacancies in the oxygen sublattice and the latter in the titanium sublattice. Up to the pressure of 60 kbar, no significant change in the crystal structure has been observed. The change in the lattice parameter with increasing pressure is unexpectedly small for both the specimens, but a minor difference between them has been observed. An initial change is larger in TiO_ than in TiO_, while in the pressure range between 10 and 60 kbar the latter shows faster decrease. The experimental results are discussed in relation to the behavior of the vacancies under high pressure