WNT signalling in prostate cancer

Genome sequencing and gene expression analyses of prostate tumours have highlighted the potential importance of genetic and epigenetic changes observed in WNT signalling pathway components in prostate tumours-particularly in the development of castration-resistant prostate cancer. WNT signalling is also important in the prostate tumour microenvironment, in which WNT proteins secreted by the tumour stroma promote resistance to therapy, and in prostate cancer stem or progenitor cells, in which WNT-β-catenin signals promote self-renewal or expansion. Preclinical studies have demonstrated the potential of inhibitors that target WNT receptor complexes at the cell membrane or that block the interaction of β-catenin with lymphoid enhancer-binding factor 1 and the androgen receptor, in preventing prostate cancer progression. Some WNT signalling inhibitors are in phase I trials, but they have yet to be tested in patients with prostate cancer

Chickpea

The narrow genetic base of cultivated chickpea warrants systematic collection, documentation and evaluation of chickpea germplasm and particularly wild Cicer species for effective and efficient use in chickpea breeding programmes. Limiting factors to crop production, possible solutions and ways to overcome them, importance of wild relatives and barriers to alien gene introgression and strategies to overcome them and traits for base broadening have been discussed. It has been clearly demonstrated that resistance to major biotic and abiotic stresses can be successfully introgressed from the primary gene pool comprising progenitor species. However, many desirable traits including high degree of resistance to multiple stresses that are present in the species belonging to secondary and tertiary gene pools can also be introgressed by using special techniques to overcome pre- and post-fertilization barriers. Besides resistance to various biotic and abiotic stresses, the yield QTLs have also been introgressed from wild Cicer species to cultivated varieties. Status and importance of molecular markers, genome mapping and genomic tools for chickpea improvement are elaborated. Because of major genes for various biotic and abiotic stresses, the transfer of agronomically important traits into elite cultivars has been made easy and practical through marker-assisted selection and marker-assisted backcross. The usefulness of molecular markers such as SSR and SNP for the construction of high-density genetic maps of chickpea and for the identification of genes/QTLs for stress resistance, quality and yield contributing traits has also been discussed

Vascularised endosteal bone tissue in armoured sauropod dinosaurs

The presence of well-vascularised, endosteal bone in the medullary region of long bones of nonavian dinosaurs has been invoked as being homologous to medullary bone, a specialised bone tissue formed during ovulation in birds. However, similar bone tissues can result as a pathological response in modern birds and in nonavian dinosaurs, and has also been reported in an immature nonavian dinosaur. Here we report on the occurrence of well-vascularised endosteally formed bone tissue in three skeletal elements of armoured titanosaur sauropods from the Upper Cretaceous of Argentina: i) within the medullary cavity of a metatarsal, ii) inside a pneumatic cavity of a posterior caudal vertebra, iii) in intra-trabecular spaces in an osteoderm. We show that considering the criteria of location, origin (or development), and histology, these endosteally derived tissues in the saltasaurine titanosaurs could be described as either medullary bone or pathological bone. Furthermore, we show that similar endosteally formed well-vascularised bone tissue is fairly widely distributed among nondinosaurian Archosauriformes, and are not restricted to long bones, but can occur in the axial, and dermal skeleton. We propose that independent evidence is required to verify whether vascularised endosteal bone tissues in extinct archosaurs are pathological or reproductive in nature.Fil: Chinsamy, Anusuya. University of Cape Town; ArgentinaFil: Cerda, Ignacio Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigación en Paleobiología y Geología; ArgentinaFil: Powell, Jaime Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo; Argentin

Longitudinal MRI contrast enhanced monitoring of early tumour development with manganese chloride (MnCl₂) and superparamagnetic iron oxide nanoparticles (SPIOs) in a CT1258 based <it>in vivo</it> model of prostate cancer

<p>Abstract</p> <p>Background</p> <p>Cell lines represent a key tool in cancer research allowing the generation of neoplasias which resemble initial tumours in <it>in-vivo</it> animal models. The characterisation of early tumour development is of major interest in order to evaluate the efficacy of therapeutic agents. Magnetic resonance imaging (MRI) based <it>in-vivo</it> characterisation allows visualisation and characterisation of tumour development in early stages prior to manual palpation. Contrast agents for MRI such as superparamagnetic iron oxide nanoparticles (SPIOs) and manganese chloride (MnCl₂) represent powerful tools for the <it>in-vivo</it> characterisation of early stage tumours. In this experimental study, we labelled prostate cancer cells with MnCl₂ or SPIOs <it>in vitro</it> and used 1 T MRI for tracing labelled cells <it>in-vitro</it> and 7 T MRI for tracking in an <it>in-vivo</it> animal model.</p> <p>Methods</p> <p>Labelling of prostate cancer cells CT1258 was established <it>in-vitro</it> with MnCl₂ and SPIOs. <it>In-vitro</it> detection of labelled cells in an agar phantom was carried out through 1 T MRI while <it>in-vivo</it> detection was performed using 7 T MRI after subcutaneous (s.c.) injection of labelled cells into NOD-Scid mice (n = 20). The animals were scanned in regular intervals until euthanization. The respective tumour volumes were analysed and corresponding tumour masses were subjected to histologic examination.</p> <p>Results</p> <p>MnCl₂<it>in-vitro</it> labelling resulted in no significant metabolic effects on proliferation and cell vitality. <it>In-vitro</it> detection-limit accounted 10⁵ cells for MnCl₂ as well as for SPIOs labelling. <it>In-vivo</it> 7 T MRI scans allowed detection of 10³ and 10⁴ cells. <it>In-vivo</it> MnCl₂ labelled cells were detectable from days 4–16 while SPIO labelling allowed detection until 4 days after s.c. injection. MnCl₂ labelled cells were highly tumourigenic in NOD-Scid mice and the tumour volume development was characterised in a time dependent manner. The amount of injected cells correlated with tumour size development and disease progression. Histological analysis of the induced tumour masses demonstrated characteristic morphologies of prostate adenocarcinoma.</p> <p>Conclusions</p> <p>To the best of our knowledge, this is the first study reporting direct <it>in-vitro</it> MnCl₂ labelling and 7 T based <it>in-vivo</it> MRI tracing of cancer cells in a model of prostate cancer. MnCl₂ labelling was found to be suitable for <it>in-vivo</it> tracing allowing long detection periods. The labelled cells kept their highly tumourigenic potential <it>in-vivo.</it> Tumour volume development was visualised prior to manual palpation allowing tumour characterisation in early stages of the disease.</p