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Hideo Yuki,1,* Takao Kamai,1,* Keiichi Kubota,2 Hideyuki Abe,1 Daisaku Nishihara,1 Tomoya Mizuno,1 Akinori Masuda,1 Hironori Betsunoh,1 Masahiro Yashi,1 Yoshitatsu Fukabori,1 Ken-Ichiro Yoshida1 1Department of Urology, 2Department of Gastroenterological Surgery, Dokkyo Medical University, Mibu, Tochigi, Japan *These authors contributed equally to this manuscript Background: Renal cell carcinoma (RCC) with sarcomatoid differentiation is invasive, refractory to treatment, and has a higher mortality. Therefore, systemic therapy is still challenging, and the curative resection of localized or locally advanced RCC with sarcomatoid differentiation is very important. Axitinib is a potent and selective second-generation vascular endothelial growth factor receptor tyrosine kinase inhibitor with improved safety and tolerability. Axitinib is generally recommended as second-line therapy for advanced RCC because the phase III axitinib versus sorafenib in advanced RCC (AXIS) trial demonstrated that it achieved longer progression-free survival than sorafenib in patients with metastatic RCC after failure of an approved first-line regimen. Methods: We present a 73-year-old man who had a large (13 cm in diameter) right RCC with sarcomatoid differentiation that directly invaded the duodenum and inferior vena cava. The patient presented with gastrointestinal bleeding, was unable to eat solid food, and had become emaciated. Thus, his classification was poor risk with anemia, hypercalcemia, and poor performance status, according to the Memorial Sloan-Kettering Cancer Center criteria. He seemed unlikely to survive if radical nephrectomy, cavotomy with thrombectomy, and pancreatoduodenectomy were performed. To reduce the tumor burden and potential operative complications, we administered axitinib as first-line neoadjuvant therapy. Results: Six weeks of treatment reduced the tumor burden without causing severe toxicities. Subsequently, radical right nephrectomy, cavotomy with thrombectomy, and pancreatoduodenectomy were performed successfully. The pathological treatment effect of axitinib was grade 2 (two-thirds necrosis). The resected tumor showed a heterogeneous reaction for phosphorylated Akt (Ser-473) by Western blotting and immunohistochemistry, indicating that parts of the tumor were sensitive to axitinib and other parts were not. Conclusion: Axitinib might be promising as preoperative or neoadjuvant therapy for locally advanced RCC (>cT3b or >cTanyN1). Keywords: renal cell carcinoma, sarcomatoid differentiation, axitinib, tyrosine kinase inhibitors, phosphorylated Akt

Trees in seasonal climates gauge winter progression to assure vital and productive blooming. However, how dormant plants asses environmental conditions remains obscure. We postulated that it involves the energetic reserves required for bloom, and therefore studied winter carbohydrate metabolism in deciduous trees. We quantified non-structural carbohydrates throughout winter in almond, peach, and pistachio trees in California and Israel and characterized winter metabolism. We constructed a carbohydrate-temperature (C–T) model that projects changes in starch and soluble carbohydrate concentrations by temperature mediated kinetics. Then, we tested the C–T model projections of bloom times by 20 years of temperature and phenology records from California. The C–T model attributes winter carbohydrate regulation in dormant trees to continuous updates of metabolic pathways. The model projects a surge in starch synthesis at the end of winter, and critically low concentrations of soluble carbohydrates, that trigger bloom. This is supported by field measurements of starch accumulation at the end of winter (˜50 mg g−1 DW in almonds) that preceded bloom by ˜10 days. The C–T model provides a physiological framework for bloom forecasts in deciduous orchards. It integrates contrasting notions of chill and heat and elucidates why abnormal winter temperatures may compromise bloom in deciduous orchards.

The dual-probe heat-pulse (DPHP) method is attractive for measuring soil thermal properties and volumetric water content. The purpose of this study was to develop and test a DPHP sensor having rigid probes made from thickwalled stainless steel tubing (2.38-mm outside diameter). The probes of this sensor are much more resistant to deflection than those of conventional DPHP sensors, decreasing measurement error caused by probe deflection during insertion into the soil. Laboratory experiments were conducted across a wide range of saturation levels with glass beads and three soils of different textures. For inferring soil properties from the proposed sensor, we applied the recently developed identical cylindrical perfect conductors (ICPC) model instead of the infinite line source (ILS) model that is typically used. The ICPC model improves solution for heat transport through the probe-soil system by accounting for the heat capacity and radius of the probes. Our results show a root mean square error of 1.4% volumetric water content and elimination of the measurement bias typically encountered with DPHP measurements. We conclude that the improved sensor, in combination with the ICPC model, provides a general, soil-independent water content estimate that is especially suitable for field soil water content monitoring because of its robust design with rigid probes. Because of its simplicity and measurements independent of soil type, we propose the presented DPHP method as an excellent alternative to other available measurement techniques for soil water content.

Archaeological village ruins discovered in the bottom of Lake Biwa should be the records of tectonic and non-tectonic movement of coastal ground and its influence on the history and development of coastal towns from the medieval ages. Recent investigations in the Naoe-senken (village) and the Shimosakahama-senken of the eastern coast of Lake Biwa revealed that liquefaction of coastal ground (soft sand) induced landslides moved into Lake Biwa. Modern cities are intensively developed until coastal line on the similar ground condition around large lakes and ponds. The archaeological and geological investigations on sub-bottom village ruins in Lake Biwa should point out the hazard risk and provide the assessment for sustainability of the modern waterfront cities. [ABSTRACT FROM AUTHOR]

The p27[SUPKip1](p27) protein is a cyclin-dependent kinase inhibitor of the transition from G1 to S phase. It has been reported that decreased p27 protein level is a negative prognostic indicator in human tumours including bladder cancer. We studied the relationship between protein levels of p27, cyclin E and Ki-67 and clinicopathological features of 145 consecutive Japanese patients with transitional cell carcinoma of the bladder using immunohistochemical staining. Low protein levels of p27 were associated with low staining of cyclin E (P = 0.0302), high Ki-67 index (P = 0.0306), poorly differentiated grade (P = 0.0006), muscle invasion (P = 0.0019) and lymph node metastsis (P = 0.0002). Low staining of cyclin E and high Ki-67 index correlated with poorly differentiated grade, muscle invasion and lymph node metastsis. Cyclin E protein levels was inversely related with Ki-67 index (P = 0.0002). Kaplan-Meier plots of survival rate in patients with low versus high p27 staining showed that low protein levels of p27 were associated with a shortened disease-free and overall survival (P < 0.0001 and P < 0.0001, respectively). Similarly, low staining of cyclin E and high Ki-67 index correlated with a shortened disease-free and overall survival. On multivariate analysis using Cox proportional hazards model, low protein levels of p27 and high Ki-67 index were independent predictors of shortened disease-free (P < 0.0001,P = 0.0031, respectively), and low protein levels of p27, low staining of cyclin E and high Ki-67 index of overall survival (P = 0.0017, P = 0.0009, P = 0.0003, respectively). In superficial bladder tumours (Ta, T1; 86 patients), significant correlations were observed between low p27 staining and high Ki-67 index and early recurrence (P = 0.0048, P = 0.0178, respectively). Among the recurrenced superficial tumours (35 patients), the tumours which remained at a low stage showed high protein levels of p27 and cyclin E, and the tumours which... [ABSTRACT FROM AUTHOR]

Objective To determine the significance of p27Kip1 (p27) for tumour behaviour and prognosis of patients with transitional cell carcinoma (TCC) of the renal pelvis and ureter. Patients and methods Using immunohistochemical staining, the relationship was evaluated between p27 protein level (low < 50%, high > 50%) and the Ki-67 labelling index (low < 30%, high > 30%) and clinicopathological features of 37 consecutive Japanese patients with TCC of the renal pelvis and ureter. Results Low levels of p27 correlated with higher tumour stage (P < 0.05) and positive lymph node metastases (P < 0.05). There was no significant association between p27 staining and the grade and tumour proliferation as assessed by the Ki-67 index. A high Ki-67 index correlated with higher grade and stage (P < 0.05). Kaplan-Meier plots of survival rate in patients with low or high p27 staining showed that low levels correlated with a shorter disease-free and overall survival (P < 0.001 and P < 0.01, respectively). Similarly, patients with a high Ki-67 index had lower disease-free and overall survival than those with a low Ki-67 index (P < 0.01 and P < 0.05, respectively). The Cox proportional hazards model showed that a low level of p27 was an independent predictor of a shorter disease-free (P < 0.01) and overall survival (P < 0.05) on univariate analysis, but not of overall survival on multivariate analysis. A high Ki-67 index was an independent prognostic marker for shorter disease-free survival on univariate and multivariate analysis (P < 0.01) and for overall survival on multivariate analysis (P < 0.05). In those with a high Ki-67 index, increased p27 staining was associated with a better prognosis than decreased staining for disease-free and overall survival (log-rank test, P < 0.01 and P < 0.05, respectively). Conclusions The finding that a low level of p27 is associated with tumour invasion and unfavourable prognosis indicates that p27 may be a useful prognostic marker for survival in upper urinary tract cancer. [ABSTRACT FROM AUTHOR]