Mir143 expression inversely correlates with nuclear ERK5 immunoreactivity in clinical prostate cancer.

BACKGROUND: Aberrant mitogen/extracellular signal-regulated kinase 5 (MEK5)-extracellular signal-regulated protein kinase 5 (ERK5)-mediated signalling has been implicated in a number of tumour types including prostate cancer (CaP). The mechanism for ERK5 activation in CaP remains to be fully elucidated. Studies have recently implicated the role of microRNA (miRNA) mir143 expression in the regulation of ERK5 expression. METHODS: We utilised a tissue microarray (TMA) of 530 CaP cores from 168 individual patients and stained for both mir143 and ERK5. These TMAs were scored by a combination of observer and automated methods. RESULTS: We observed a strong inverse relation between ERK5 and mir143, which manifested itself most strongly in the subgroup of 417 cores with non-zero mir143 and ERK5 immunoreactivity, or with only one of mir143 or ERK5 being zero (cc=0.2558 and P<0.0001). Mir143 neither correlate with Gleason scores or prostate-specific antigen levels, nor was it a predictor of disease-specific survival on univariate analysis. CONCLUSION: Although the mechanism for ERK5 activation in CaP remains to be fully elucidated, we have further validated the potential role of mir143 in regulating ERK5 levels in the clinical context. In addition, we demonstrate that the automated counting method for nuclear ERK5 is a clinically useful alterative to observer counting method in patient stratification in the context of ERK5 targeting therapy.

Estimation of proximate composition, micronutrients and phytochemical compounds in traditional vegetables from Andaman and Nicobar Islands.

In present study, 10 preferred traditional vegetables from Andaman and Nicobar Islands, India, were analysed for nutritional profiles. Moisture content in their edible parts ranged from 83.43 to 94.78%. Maximum ash content was recorded in Portulaca oleracea, crude protein in Colocasia esculenta, crude fibre in Eryngium foetidum and fat in E. foetidum. Phosphorus was maximum in Ipomea aquatica, potassium in C. esculenta, zinc, calcium and manganese in Centella asiatica, copper in Sauropus androgynous, sodium and iron in P. oleracea, magnesium in Amaranthus viridi and cobalt in C. esculenta. Maximum polyphenol was recorded in Hibiscus sabdariffa, carotenoids in A. viridi, ascorbic acid in Saursops androgynus, anthocyanin in C. esculenta and chlorophyll in S. androgynus. Antioxidant activity was maximum in P. oleracea. Positive correlation was observed between polyphenol and tannin content and also between antioxidant activity and photochemicals. The developed nutritional profiles is being used in health and nutrition related schemes in Islands.

Ras mutation cooperates with ß-catenin activation to drive bladder tumourigenesis.

Mutations in the Ras family of proteins (predominantly in H-Ras) occur in approximately 40% of urothelial cell carcinoma (UCC). However, relatively little is known about subsequent mutations/pathway alterations that allow tumour progression. Indeed, expressing mutant H-Ras within the mouse bladder does not lead to tumour formation, unless this is expressed at high levels. The Wnt signalling pathway is deregulated in approximately 25% of UCC, so we examined if this correlated with the activation of MAPK signalling in human UCC and found a significant correlation. To test the functional significance of this association we examined the impact of combining Ras mutation (H-Ras(Q61L) or K-Ras(G12D)) with an activating ß-catenin mutation within the mouse bladder using Cre-LoxP technology. Although alone, neither Ras mutation nor ß-catenin activation led to UCC (within 12 months), mice carrying both mutations rapidly developed UCC. Mechanistically this was associated with reduced levels of p21 with dependence on the MAPK signalling pathway. Moreover, tumours from these mice were sensitive to MEK inhibition. Importantly, in human UCC there was a negative correlation between levels of p-ERK and p21 suggesting that p21 accumulation may block tumour progression following Ras mutation. Taken together these data definitively show Ras pathway activation strongly cooperates with Wnt signalling to drive UCC in vivo.

ß-Catenin activation synergizes with PTEN loss to cause bladder cancer formation.

Although deregulation of the Wnt signalling pathway has been implicated in urothelial cell carcinoma (UCC), the functional significance is unknown. To test its importance, we have targeted expression of an activated form of ß-catenin to the urothelium of transgenic mice using Cre-Lox technology (UroIICRE(+) ß-catenin(exon3/+)). Expression of this activated form of ß-catenin led to the formation of localized hyperproliferative lesions by 3 months, which did not progress to malignancy. These lesions were characterized by a marked increase of the phosphatase and tensin homologue (PTEN) tumour suppressor protein. This appears to be a direct consequence of activating Wnt signalling in the bladder as conditional deletion of the adenomatous polyposis coli (Apc) gene within the adult bladder led rapidly to coincident ß-catenin and PTEN expression. This PTEN expression blocked proliferation. Next, we combined PTEN deficiency with ß-catenin activation and found that this caused papillary UCC. These tumours had increased pAKT signalling and were dependent on mammalian target of rapamycin (mTOR). Importantly, in human UCC, there was a significant correlation between high levels of ß-catenin and pAKT (and low levels of PTEN). Taken together these data show that deregulated Wnt signalling has a critical role in promoting UCC, and suggests that human UCC that have high levels of Wnt and PI3 kinase signalling may be responsive to mTOR inhibition.

Urolithiasis in Manipur (north eastern region of India). Incidence and chemical composition of stones.

The incidence of urolithiasis in Manipur is very high. From hospital records for a period of 7 years and 3 months, it was observed to be 11.6% of all general surgery cases in the General Hospital, Imphal. This is alarmingly high. The social, eating, drinking, and living habits are different among the three major populations in this state. The prevalence was minimal among Tribals. Compared to them the prevalence was about one and one half times higher among Muslims (also called Pangals) and seven times higher among Hindus. Surprisingly, the incidence of renal calcalus was higher in females. One hundred ninety-six stones were studied by wet chemical analysis. Calcium and oxalate were present in all stones. Phosphate was present in 194 stones and uric acid (including urate) was present in 146 stones.