Notch signaling augments the canonical Wnt pathway to specify the size of the otic placode

The inner ear derives from a patch of ectoderm defined by expression of the transcription factor Pax2. We recently showed that this Pax2^+ ectoderm gives rise not only to the otic placode but also to the surrounding cranial epidermis, and that Wnt signaling mediates this placode-epidermis fate decision. We now present evidence for reciprocal interactions between the Wnt and Notch signaling pathways during inner ear induction. Activation of Notch1 in Pax2+ ectoderm expands the placodal epithelium at the expense of cranial epidermis, whereas loss of Notch1 leads to a reduction in the size of the otic placode. We show that Wnt signaling positively regulates Notch pathway genes such as Jag1, Notch1 and Hes1, and we have used transgenic Wnt reporter mice to show that Notch signaling can modulate the canonical Wnt pathway. Gain- and loss-of-function mutations in the Notch and Wnt pathways reveal that some aspects of otic placode development - such as Pax8 expression and the morphological thickening of the placode - can be regulated independently by either Notch or Wnt signals. Our results suggest that Wnt signaling specifies the size of the otic placode in two ways, by directly upregulating a subset of otic genes, and by positively regulating components of the Notch signaling pathway, which then act to augment Wnt signaling

Surgical Treatment of a Giant Liposarcoma in a Japanese Man

We report a case of a rapidly progressing giant retroperitoneal liposarcoma weighing 22 kg in a 41-year-old Japanese man, successfully treated with surgical excision. To our knowledge, this is the largest liposarcoma in the Japanese population reported in the literature

A case of metastatic cancer with markedly elevated PSA level that was not detected by repeat prostate biopsy

BACKGROUND: Prostate-specific antigen (PSA) is a widely used specific tumor marker for prostate cancer. We experienced a case of metastatic prostate cancer that was difficult to detect by repeat prostate biopsy despite a markedly elevated serum PSA level. CASE PRESENTATION: A 64-year-old man was referred to our hospital with lumbar back pain and an elevated serum PSA level of 2036 ng/mL. Computed tomography, bone scintigraphy, and magnetic resonance imaging showed systemic lymph node and osteoblastic bone metastases. Digital rectal examination revealed a small, soft prostate without nodules. Ten-core transrectal prostate biopsy yielded negative results. Androgen deprivation therapy (ADT) was started because of the patient’s severe symptoms. Twelve-core repeat transrectal prostate biopsy performed 2 months later, and transurethral resection biopsy performed 5 months later, both yielded negative results. The patient refused further cancer screening because ADT effectively relieved his symptoms. His PSA level initially decreased to 4.8 ng/mL, but he developed castration-resistant prostate cancer 7 months after starting ADT. He died 21 months after the initial prostate biopsy from disseminated intravascular coagulation. CONCLUSION: CUP remains a considerable challenge in clinical oncology. Biopsies of metastatic lesions and multimodal approaches were helpful in this case

Serum N

Background. The aim of this study is to evaluate the usefulness of serum N-glycan profiling for prognosis in hemodialysis patients. Methods. Serum N-glycan analysis was performed in 100 hemodialysis patients in June 2008 using the glycoblotting method, which allows high-throughput, comprehensive, and quantitative N-glycan analysis. All patients were longitudinally followed up for 5 years. To evaluate the independent predictors for prognosis, patients' background, blood biochemistry, and N-glycans intensity were analyzed using Cox regression multivariate analysis. Selected N-glycans and independent factors were evaluated using the log-rank test with the Kaplan-Meier method to identify the predictive indicators for prognosis. Each patient was categorized according to the number of risk factors to evaluate the predictive potential of the risk criteria for prognosis. Results. In total, 56 N-glycan types were identified in the hemodialysis patients. Cox regression multivariate analysis showed cardiovascular events, body mass index, maximum intima media thickness, and the serum N-glycan intensity of peak number 49 were predictive indicators for overall survival. Risk classification according to the number of independent risk factors revealed significantly poor survival by increasing the number of risk factors. Conclusions. Serum N-glycan profiling may have a potential to predict prognosis in patients undergoing hemodialysis

Preoperative Butyrylcholinesterase Level as an Independent Predictor of Overall Survival in Clear Cell Renal Cell Carcinoma Patients Treated with Nephrectomy

The prognostic factors for the overall survival (OS) of clear cell renal cell carcinoma (ccRCC) patients treated with nephrectomy are not well defined. In the present study, we investigated the prognostic significance of preoperative butyrylcholinesterase (BChE) levels in 400 ccRCC patients undergoing radical or partial nephrectomy from 1992 to 2013 at our institution. Univariate and multivariate analyses were performed to determine the clinical factors associated with OS. Among the enrolled patients, 302 were diagnosed with organ-confined disease only (T1-2N0M0), 16 with lymph node metastases, and 56 with distant metastases. The median preoperative BChE level was 250 U/L (normal range, 168–470 U/L), and median follow-up period was 36 months. The 3-year OS rate in patients with preoperative BChE levels of ≥100 U/L was significantly higher than in those with levels of <100 U/L (89.3% versus 77.7%, P=0.004). On univariate analysis, performance status; anemia; hypoalbuminemia; preoperative levels of BChE, corrected calcium, and C-reactive protein; and distant metastasis status were significantly associated with OS. Multivariate analysis revealed that preoperative BChE levels and distant metastasis status were significantly associated with OS. Our findings suggest a possible role of preoperative BChE levels as an independent predictor of OS after nephrectomy in ccRCC patients

Effect of an Oral Adsorbent, AST-120, on Dialysis Initiation and Survival in Patients with Chronic Kidney Disease

The oral adsorbent AST-120 has the potential to delay dialysis initiation and improve survival of patients on dialysis. We evaluated the effect of AST-120 on dialysis initiation and its potential to improve survival in patients with chronic kidney disease. The present retrospective pair-matched study included 560 patients, grouped according to whether or not they received AST-120 before dialysis (AST-120 and non-AST-120 groups). The cumulative dialysis initiation free rate and survival rate were compared by the Kaplan-Meier method. Multivariate analysis was used to determine the impact of AST-120 on dialysis initiation. Our results showed significant differences in the 12- and 24-month dialysis initiation free rate (P < 0.001), although no significant difference was observed in the survival rate between the two groups. In conclusion, AST-120 delays dialysis initiation in chronic kidney disease (CKD) patients but has no effect on survival. AST-120 is an effective therapy for delaying the progression of CKD

Efficacy of SMART Stent Placement for Salvage Angioplasty in Hemodialysis Patients with Recurrent Vascular Access Stenosis

Vascular access stenosis is a major complication in hemodialysis patients. We prospectively observed 50 patients in whom 50 nitinol shape-memory alloy-recoverable technology (SMART) stents were used as salvage therapy for recurrent peripheral venous stenosis. Twenty-five stents each were deployed in native arteriovenous fistula (AVF) and synthetic arteriovenous polyurethane graft (AVG) cases. Vascular access patency rates were calculated by Kaplan-Meier analysis. The primary patency rates in AVF versus AVG at 3, 6, and 12 months were 80.3% versus 75.6%, 64.9% versus 28.3%, and 32.3% versus 18.9%, respectively. The secondary patency rates in AVF versus AVG at 3, 6, and 12 months were 88.5% versus 75.5%, 82.6% versus 61.8%, and 74.4% versus 61.8%, respectively. Although there were no statistically significant difference in patency between AVF and AVG, AVG showed poor tendency in primary and secondary patency. The usefulness of SMART stents was limited in a short period of time in hemodialysis patients with recurrent vascular access stenosis

Newly characterized interaction stabilizes DNA structure: oligoethylene glycols stabilize G-quadruplexes CH–π interactions

Oligoethylene glycols are used as crowding agents in experiments that aim to understand the effects of intracellular environments on DNAs. Moreover, DNAs with covalently attached oligoethylene glycols are used as cargo carriers for drug delivery systems. To investigate how oligoethylene glycols interact with DNAs, we incorporated deoxythymidine modified with oligoethylene glycols of different lengths, such as tetraethylene glycol (TEG), into DNAs that form antiparallel G-quadruplex or hairpin structures such that the modified residues were incorporated into loop regions. Thermodynamic analysis showed that because of enthalpic differences, the modified G-quadruplexes were stable and the hairpin structures were slightly unstable relative to unmodified DNA. The stability of G-quadruplexes increased with increasing length of the ethylene oxides and the number of deoxythymidines modified with ethylene glycols in the G-quadruplex. Nuclear magnetic resonance analyses and molecular dynamics calculations suggest that TEG interacts with bases in the G-quartet and loop via CH-pi and lone pair-pi interactions, although it was previously assumed that oligoethylene glycols do not directly interact with DNAs. The results suggest that numerous cellular co-solutes likely affect DNA function through these CH-pi and lone pair-pi interactions

Skin Perfusion Pressure Is a Prognostic Factor in Hemodialysis Patients

Peripheral arterial disease (PAD) is common in hemodialysis patients and predicts a poor prognosis. We conducted a prospective cohort study to identify risk factors for PAD including skin perfusion pressure (SPP) in hemodialysis patients. The cohort included 373 hemodialysis patients among 548 patients who received hemodialysis at Oyokyo Kidney Research Institute, Hirosaki, Japan from August 2008 to December 2010. The endpoints were lower limb survival (peripheral angioplasty or amputation events) and overall survival of 2 years. Our results showed that <70 mmHg SPP was a poor prognosis for the lower limb survival and overall survival. We also identified age, history of cardiovascular disease, presence of diabetes mellitus, smoking history, and SPP < 70 mmHg as independent risk factors for lower limb survival and overall survival. Then, we constructed risk criteria using the significantly independent risk factors. We can clearly stratify lower limb survival and overall survival of the hemodialysis patients into 3 groups. Although the observation period is short, we conclude that SPP value has the potential to be a risk factor that predicts both lower limb survival and the prognosis of hemodialysis patients