Molecular characterization of Miraflores peach variety and relatives using SSRs

The definitive version is published in: http://www.sciencedirect.com/science/journal/03044238Some traditional peach varieties, originated from the region of Aragón (Spain), were analysed by SSRs (Simple Sequence Repeats). The aim of this research was to characterize 19 clones related to ‘Miraflores’ variety, with unknown pedigrees, to assess their genetic diversity and to elucidate their possible relationships with 10 traditional peach varieties. Twenty SSR primer pairs with high levels of polymorphism, which have been previously developed for peach, were used in this study. A total of 46 alleles were obtained for all the microsatellites studied, ranging from one to six alleles per locus, with a mean value of 2.3 alleles per locus. Fourteen SSRs were polymorphic in the set of varieties studied and permitted to distinguish 16 different genotypes out of the 30 initially studied, although fourteen ‘Miraflores’ clones showed identical gel profiles. The genetic distance matrix was used to construct Neighbor joining cluster and to perform principal coordinate analysis which allowed the arrangement of all the genotypes according to their genetic relationships. The genetic relationships among these traditional peach varieties, and in particular among ‘Miraflores’ clones are discussed. The obtained results confirm that microsatellite markers are very useful for these purposes.We are thankful to T.N. Zhebentyayeva and G.L. Reighard for helpful comments on the manuscript. This research was funded by CICYT (Comisión Interministerial de Ciencia y Tecnología, AGL2002-04219 and AGL 2005-05533), INIA (Instituto Nacional de Investigación y Tecnología Agraria y Alimentación, RF03-014-C2), Bilateral Spain-France (HF03-273) and DGA (A28, A44) projects and co-funded by the European Regional Development Fund. M. Bouhadida was supported by a fellowship from the AECI (Agencia Española de Cooperación Internacional) of the Spanish Ministry of Foreign Affairs.Peer reviewe

Changes in plasma biomarkers following treatment with cabozantinib in metastatic castration-resistant prostate cancer: a post hoc analysis of an extension cohort of a phase II trial

BACKGROUND: Cabozantinib is an orally available inhibitor of tyrosine kinases including VEGFR2 and c-MET. We performed a post hoc analysis to find associations between select plasma biomarkers and treatment response in patients (pts) with metastatic castration resistant prostate cancer (mCRPC) who received cabozantinib 100 mg daily as part of a phase 2 non-randomized expansion cohort (NCT00940225). METHODS: Plasma samples were collected at baseline, 6 weeks and at time of maximal response from 81 mCRPC pts with bone metastases, of which 33 also had measurable soft-tissue disease. Levels of 27 biomarkers were measured in duplicate using enzyme-linked immunosorbent assay. Spearman correlation coefficients were calculated for the association between biomarker levels or their change on treatment and either bone scan response (BSR) or soft tissue response according to RECIST. RESULTS: A BSR and RECIST response were seen in 66/81 pts (81 %) and 6/33 pts (18 %) respectively. No significant associations were found between any biomarker at any time point and either type of response. Plasma concentrations of VEGFA, FLT3L, c-MET, AXL, Gas6A, bone-specific alkaline phosphatase, interleukin-8 and the hypoxia markers CA9 and clusterin significantly increased during treatment with cabozantinib irrespective of response. The plasma concentrations of VEGFR2, Trap5b, Angiopoietin-2, TIMP-2 and TIE-2 significantly decreased during treatment with caboznatinib. CONCLUSIONS: Our data did not reveal plasma biomarkers associated with response to cabozantinib. The observed alterations in several biomarkers during treatment with cabozantinib may provide insights on the effects of cabozantinib on tumor cells and on tumor micro-environment and may help point to potential co-targeting approaches

Molecular targeting of antiangiogenic factor 16K hPRL inhibits oxygen-induced retinopathy in mice

PURPOSE. To examine the ability and mechanism of the 16 kDa N-terminal fragment of human prolactin (16K hPRL) in the inhibition of abnormal retinal neovascularization. METHODS. The 16K hPRL-encoding sequence was inserted into an adenoviral vector (16K-Ad). Western blot analysis verified the expression of 16K hPRL and inhibition of proliferation, confirming functional activity of the 16K hPRL in virus-infected adult bovine aortic endothelial (ABAE) cells. 16K hPRL inhibited retinal neovascularization in a mouse model of oxygen-induced retinopathy. The ability of recombinant 16K hPRL expressed in E. coli (r16K hPRL) was compared to that of endostatin in inducing apoptosis of cultured human retinal endothelial cells (HREC). RESULTS. 16K was expressed in virus-infected ABAE cells and resulted in a dose-dependent inhibition of cell proliferation. Eyes injected with 16K-Ad showed a reduction in preretinal neovascularization of 82.3 +/- 9.3% (P < 0.00001) when compared to uninjected controls. r16K hPRL was 100 times more potent than endostatin in inducing apoptosis in HRECs. CONCLUSIONS. Intravitreal administration of 16K hPRL inhibited neovascularization in the mouse model of oxygen-induced retinopathy. 16K hPRL stimulated apoptosis in HRECs and inhibited cell proliferation in ABAE cells. These results suggested a potential therapeutic role for 16K hPRL in the treatment of proliferative retinopathies

Opposing Actions of Intact and N-Terminal Fragments of the Human Prolactin/Growth Hormone Family Members on Angiogenesis: An Efficient Mechanism for the Regulation of Angiogenesis

Angiogenesis, the process of development of a new microvasculature, is regulated by a balance of positive and negative factors. We show both in vivo and in vitro that the members of the human prolactin/growth hormone family, i.e., human prolactin, human growth hormone, human placental lactogen, and human growth hormone variant are angiogenic whereas their respective 16-kDa N-terminal fragments are antiangiogenic. The opposite actions are regulated in part via activation or inhibition of mitogen-activated protein kinase signaling pathway. In addition, the N-terminal fragments stimulate expression of type 1 plasminogen activator inhibitor whereas the intact molecules have no effect, an observation consistent with the fragments acting via separate receptors. The concept that a single molecule encodes both angiogenic and antiangiogenic peptides represents an efficient model for regulating the balance of positive and negative factors controlling angiogenesis. This hypothesis has potential physiological importance for the control of the vascular connection between the fetal and maternal circulations in the placenta, where human prolactin, human placental lactogen, and human growth hormone variant are expressed

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