Urothelial carcinoma usually shows divergent differentiation and variant histology with squamous and glandular morphology being most common. In this report, we present a case of divergent malignant ...melanocytic differentiation in a high-grade urothelial carcinoma. A 98-year-old East Asian woman with an anterior bladder wall mass underwent resection, which revealed a high-grade poorly differentiated tumor. A minor component of high-grade papillary urothelial carcinoma and carcinoma in situ is also present. The majority of the tumor cells are morphologically and immunohistochemically consistent with melanoma, a minority of cells are positive for urothelial markers, and rare cells coexpress both melanocytic and urothelial markers. Cells that express melanocytic markers or urothelial markers are intimately admixed together. Taken together, a diagnosis of high-grade urothelial carcinoma with malignant melanocytic differentiation was rendered. This is the first report in the literature of malignant melanocytic differentiation in a high-grade urothelial carcinoma, a finding that may have important diagnostic and therapeutic implications.
Lipid rafts are cholesterol- and sphingolipid-enriched microdomains in cell membranes that regulate phosphorylation cascades originating from membrane-bound proteins. In this study, we tested whether ...alteration of the cholesterol content of lipid rafts in prostate cancer (PCa) cell membranes affects cell survival mechanisms in vitro and in vivo. Simvastatin, a cholesterol synthesis inhibitor, lowered raft cholesterol content, inhibited Akt1 serine-threonine kinase (protein kinase Balpha)/protein kinase B (Akt/PKB) pathway signaling, and induced apoptosis in caveolin- and PTEN-negative LNCaP PCa cells. Replenishing cell membranes with cholesterol reversed these inhibitory and apoptotic effects. Cholesterol also potentiated Akt activation in normal prostate epithelial cells, which were resistant to the apoptotic effects of simvastatin. Elevation of circulating cholesterol in SCID mice increased the cholesterol content and the extent of protein tyrosine phosphorylation in lipid rafts isolated from LNCaP/sHB xenograft tumors. Cholesterol elevation also promoted tumor growth, increased phosphorylation of Akt, and reduced apoptosis in the xenografts. Our results implicate membrane cholesterol in Akt signaling in both normal and malignant cells and provide evidence that PCa cells can become dependent on a cholesterol-regulated Akt pathway for cell survival.
The lack of snow cover due to winter climate change has great potential to impact winter soil nitrogen cycling in boreal forests. A snow manipulation was conducted in a Tibetan spruce forest to ...explore the effects of snow absence on winter soil nitrogen dynamics by shelter method. Snow absence on average reduced soil temperatures at the depths of 0cm and 5cm by 1.44°C and 0.33°C, respectively, throughout the winter. Moreover, snow absence increased soil frost and freeze-thaw cycles. Soil net nitrogen mineralization and labile nitrogen pools (ammonium, nitrate and dissolved organic nitrogen) were higher in the snow absence plots compared to control plots. Snow absence increased soil microbial biomass carbon but did not affect microbial biomass nitrogen. Nevertheless, soil enzyme activities involved in nitrogen cycles were often lowered by snow absence over the winter. The results noted in this study suggest that warming-induced absence in seasonal snowpack may stimulate winter soil nitrogen availabilities by changing soil microhabitats, which has important implications for soil biogeochemical cycles in the subalpine forest ecosystems on the eastern Tibetan Plateau.
•Snow absence decreased soil temperatures but increased soil frost and freeze-thaw cycles;•Snow absence stimulated winter soil net nitrogen mineralization and availabilities of Tibetan spruce forest;•Snow absence lowered soil enzyme activities involved in nitrogen cycles during the snow-covered period.
Home-field advantage (HFA) encompasses all the processes leading to faster litter decomposition in the ‘home’ environment compared to that of ‘away’ environments. To determine the occurrence of HFA ...in a forest and adjacent clear-cut, we set up a reciprocal litter decomposition experiment within the forest and clear-cut for two soil types (Cambisols and Gleysols) in temperate Germany. The forest was dominated by Norway spruce (Picea abies), whereas forest regeneration of European Beech (Fagus sylvatica) after clearcutting was encouraged. Our observation that Norway spruce decomposed faster than European beech in 70-yr-old spruce forest was most likely related to specialized litter-soil interaction under existing spruce, leading to an HFA. Elevated soil moisture and temperature, and promoted litter N release, indicated the rapid change of soil-litter affinity of the original spruce forest even after a short-term regeneration following clearcutting, resulting in faster beech decomposition, particularly in moisture- and nutrient-deficient Cambisols. The divergence between forest and clear-cut in the Cambisol of their litter δ15N values beyond nine months implied litter N decomposition was only initially independent of soil and residual C status. We conclude that clearcutting modifies the litter-field affinity and helps promote the establishment or regeneration of European beech in this and similar forest mountain upland areas.
We report the phenotype of mice with targeted disruption of the Trpv6 (Trpv6 KO) epithelial calcium channel. The mice exhibit disordered Ca2+ homeostasis, including defective intestinal Ca2+ ...absorption, increased urinary Ca2+ excretion, decreased BMD, deficient weight gain, and reduced fertility. Although our Trpv6 KO affects the closely adjacent EphB6 gene, the phenotype reported here is not related to EphB6 dysfunction.
Introduction: The mechanisms underlying intestinal Ca2+ absorption are crucial for overall Ca2+ homeostasis, because diet is the only source of all new Ca2+ in the body. Trpv6 encodes a Ca2+‐permeable cation channel responsible for vitamin D–dependent intestinal Ca2+ absorption. Trpv6 is expressed in the intestine and also in the skin, placenta, kidney, and exocrine organs.
Materials and Methods: To determine the in vivo function of TRPV6, we generated mice with targeted disruption of the Trpv6 (Trpv6 KO) gene.
Results: Trpv6 KO mice are viable but exhibit disordered Ca2+ homeostasis, including a 60% decrease in intestinal Ca2+ absorption, deficient weight gain, decreased BMD, and reduced fertility. When kept on a regular (1% Ca2+) diet, Trpv6 KO mice have deficient intestinal Ca2+ absorption, despite elevated levels of serum PTH (3.8‐fold) and 1,25‐dihydroxyvitamin D (2.4‐fold). They also have decreased urinary osmolality and increased Ca2+ excretion. Their serum Ca2+ is normal, but when challenged with a low (0.25%) Ca2+ diet, Trpv6 KO mice fail to further increase serum PTH and vitamin D, ultimately developing hypocalcemia. Trpv6 KO mice have normal urinary deoxypyridinoline excretion, although exhibiting a 9.3% reduction in femoral mineral density at 2 months of age, which is not restored by treatment for 1 month with a high (2%) Ca2+ “rescue” diet. In addition to their deranged Ca2+ homeostasis, the skin of Trpv6 KO mice has fewer and thinner layers of stratum corneum, decreased total Ca2+ content, and loss of the normal Ca2+ gradient. Twenty percent of all Trpv6 KO animals develop alopecia and dermatitis.
Conclusions: Trpv6 KO mice exhibit an array of abnormalities in multiple tissues/organs. At least some of these are caused by tissue‐specific mechanisms. In addition, the kidneys and bones of Trpv6 KO mice do not respond to their elevated levels of PTH and 1,25‐dihydroxyvitamin D. These data indicate that the TRPV6 channel plays an important role in Ca2+ homeostasis and in other tissues not directly involved in this process.
Diabetes has become a major public health problem in China. Support of patient self-management is a key component of effective diabetes care and improved patient outcomes. A series of peer-led ...community-based disease-specific self-management programs including diabetes have been widely disseminated in urban communities of Shanghai since 1999. However, the strategy of using trained lay leaders to support patient self-management faces challenges in rural communities in Shanghai. This study developed a Chinese diabetes group visit program as an alternative approach to support patient self-management and examined its effectiveness on self-management behaviors, self-efficacy and health status for patients with type 2 diabetes in rural communities of Shanghai.
208 patients with type 2 diabetes aged 35-80 years were randomly assigned to the intervention group (n=119) of 12 monthly group visit sessions or to a control group (n=89) of usual care. The trial was undertaken in two rural communities in Shanghai, China. Randomization and allocation to study group were carried out by using a random number table. Analysis of covariance was used to compare changes in the 17 self-management behavior, self-efficacy and health status related variables in two groups at 12 months' follow-up based on 176 patients (n=98; n=78).
Compared with controls, the intervention patients, on average, increased their duration of aerobic exercise by more than 40 minutes per week (p=0.001); had significant increase of 0.71 in mean score on self-efficacy to manage diabetes (p=0.02); and had significant improvements in measures of illness intrusiveness and systolic blood pressure. The intervention patients attended an average of 10.1 of the 12 program sessions with 75.6% of them attended 10 and more sessions.
The Chinese diabetes group visit model is a feasible, acceptable and effective alternative for supporting diabetes patient self-management in Chinese rural communities. The model requires larger studies to determine its effect on blood glucose control and health care utilization.
ISRCTN87909028.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
How forest management practice impacts the temperature response of soil carbon decomposition remains unclear in Tibetan boreal forests. Here, an experiment was conducted to compare soil carbon ...decomposition of two layers (organic and mineral) in three Tibetan forests (natural forest, NF; secondary forest, SF; spruce plantation, PF). Soils were incubated at two temperatures (10 °C and 20 °C) for 219 days. Increased temperature often stimulated carbon decomposition rates of organic layer but did not affect them in the mineral soils. Soil carbon decomposition rates in the organic layer followed a pattern of NF > SF > PF over the incubation period. Regardless of forest type, soil carbon decomposition rates and temperature coefficient (Q
) were higher in the organic layers compared to mineral soils. Moreover, forest type conversion increased Q
values in each soil layer. Taken together, our results suggest that forest management practice has much stronger impacts on biochemical properties in the organic layers relative to mineral soils. Moreover, the temperature responses of soil carbon decomposition depend largely on forest management practice and soil layer in this specific area.
Progress has been made in applying genetic information to disease management in the postgenomic era, and precision medicine is emerging in prostate cancer management. The prostate health index, the ...4-kallikrein (4K) score, and the PCA3, TMPRSS2- ERG, and Prostarix tests have potential for refining prostate cancer screening in conjunction with traditional prostate-specific antigen testing. The Confirm MDx and PCA3 tests have shown promise in identifying men who need be rebiopsied after a primary negative biopsy. Oncotype DX, Prolaris, the biopsy-based Decipher prostate cancer test, and ProMark may improve predictive risk stratification in addition to the traditional Gleason score and tumor stage. Decipher and Prolaris may predict biochemical recurrence and metastasis after radical prostatectomy and possibly help identify patients who need adjuvant therapy. Androgen receptor splice variant 7 appears effective in guiding the selection of second hormonal manipulation with abiraterone or enzalutamide versus chemotherapy when treating metastatic castration-resistant prostate cancer.
Litter decomposition plays a critical role in regulating biogeochemical cycles in terrestrial ecosystems and is profoundly impacted by increasing atmospheric nitrogen (N) deposition. Here, a N ...manipulation experiment was conducted to explore the effects of N additions (0 kg N ha−1 yr−1, 20 kg N ha−1 yr−1 and 40 kg N ha−1 yr−1) on decay rates and nutrients release of two contrasting species, the evergreen and nutrient-poor Michelia wilsonii and the deciduous and nutrient-rich Camptotheca acuminata, using a litterbag approach at the western edge of the Sichuan Basin of China. The decay rate and the mineralization of N and phosphorus (P) was faster in nutrient-rich C. acuminata litter than in nutrient-poor M. wilsonii litter, regardless of N regimes. N additions tended to decrease the decay constant (k value) in M. wilsonii litter, but had no effect on C. acuminata litter. N additions had no significant effects on carbon (C) release of both litter types. N additions showed negative effects on N and P release of M. wilsonii litter, particularly in the late decomposition stage. Moreover, for C. acuminata litter, N additions did not affect N release, but retarded P release in the late stage. N additions did not affect the C:N ratio in both litter types. However, N additions—especially high-N addition treatments—tended to reduce C:P and N:P ratios in both species. The effect of N addition on N and P remaining was stronger in M. wilsonii litter than in C. acuminata litter. The results of this study indicate that N additions retarded the nutrients release of two foliar litters. Thus, rising N deposition might favor the retention of N and P via litter decomposition in this specific area experiencing significant N deposition.
Although cholesterol accumulation in tumors was first reported in the early20th century, the mechanistic implications of this observation are still obscure. Here we report that caveolin-negative ...human prostate cancer (LNCaP) cells contain cholesterol-rich lipid rafts that mediate epidermal growth factor (EGF)-induced and constitutive signaling through the Akt1 serine-threonine kinase. EGF receptor and Akt1 phosphorylation were inhibited and autonomous cell survival was reduced when the rafts were disrupted. Reconstitution of the rafts with cholesterol restored EGF receptor-->Akt1 axis signaling and cytoprotection from a phosphoinositide 3-kinase-dependent apoptotic signal. These results suggest that cholesterol present in membrane microdomains is a prominent mediator of survival in prostate cancer cells.
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