Copper uptake, accumulation and physiological changes in adult grapevines in response to excess copper in soil.

Publicada online em 24 de setembro

Ewing's sarcoma: Analysis of single nucleotide polymorphism in the EWS gene

AbstractWe aimed to investigate single nucleotide polymorphisms (SNPs) in the EWS gene breaking region in order to analyze Ewing's sarcoma susceptibility. The SNPs were investigated in a healthy subject population and in Ewing's sarcoma patients from Southern Brazil. Genotyping was performed by TaqMan® assay for allelic discrimination using Real-Time PCR. The analysis of incidence of SNPs or different SNP-arrangements revealed a higher presence of homozygote TT-rs4820804 in Ewing's sarcoma patients (p=0.02; Chi Square Test). About 300bp from the rs4820804 SNP lies a palindromic hexamer (5′-GCTAGC-3′) and three nucleotides (GTC), which were previously identified to be in close vicinity of the breakpoint junction in both EWS and FLI1 genes. This DNA segment surrounding the rs4820804 SNP is likely to indicate a breakpoint region. If the T-rs4820804 allele predisposes a DNA fragment to breakage, homozygotes (TT-rs4820804) would have double the chance of having a chromosome break, increasing the chances for a translocation to occur. In conclusion, the TT-rs4820804 EWS genotype can be associated with Ewing's sarcoma and the SNP rs4820804 can be a candidate marker to understand Ewing's sarcoma susceptibility

BDNF/TrkB Signaling as a Potential Novel Target in Pediatric Brain Tumors: Anticancer Activity of Selective TrkB Inhibition in Medulloblastoma Cells

Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Deregulation of brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) signaling has been associated with increased proliferative capabilities, invasiveness, and chemoresistance in several types of cancer. However, the relevance of this pathway in MB remains unknown. Here, we show that the selective TrkB inhibitor N-[2-[[(hexahydro-2-oxo-1H-azepin-3-yl)amino]carbonyl]phenyl]-benzo[b]thiophene-2-carboxamide (ANA-12) markedly reduced the viability and survival of human cell lines representative of different MB molecular subgroups. These findings provide the first evidence supporting further investigation of TrkB inhibition as a potential novel strategy for MB treatment

Use of phosphorus fertilization and mycorrhization as strategies for reducingcopper toxicity in young grapevines.

Established vineyard soils may have high copper (Cu) contents due to the ongoing foliar applications of copper-based fungicides. In viticulture, the replacement of old vineyards with new vines is common practice, however,limited by Cu excess in soil and its toxicity to young grapevines. The application of phosphorus (P) and ar-buscular mycorrhizal fungi (AMF) inoculation are potential strategies to reduce Cu toxicity to young grapevines.This study aimed to assess the effects of phosphorus fertilization and AMF (Rhizophagus clarus) inoculation ongrowth and physiological parameters of young grapevines grown in soil with high Cu content. The experimentwas conducted in a greenhouse, where natural grassland soil was artificially contaminated by the addition of60 mg kg−1Cu. The soils were treated with and without AMF inoculation, combined with additions of 0, 40 and100 mg P kg−1. After 90 days of cultivation, grapevine plants were assessed for chlorophyllafluorescence,photosynthetic pigment contents, superoxide dismutase (SOD) activity, plant height, plant biomass, and con-centrations of Cu and P in roots and shoots. Phosphorus fertilization promoted increases in seedling growth(related to the increase of total P concentration in roots and shoots), soluble Pi concentration in leaves, and thequantum yield of the PSII (YII) (associated with a reduction in shoot Cu concentration). The AMF inoculationincreased the concentration of P in roots and shoots, soluble Pi in leaves and electron transport rate (ETR).Phosphorus fertilization and inoculation of grapevines with AMF are strategies capable of reducing Cu toxicity inyoung grapevines

Fine-Tuning Roles of Endogenous Brain-Derived Neurotrophic Factor, TrkB and Sortilin in Colorectal Cancer Cell Survival

International audienceBACKGROUND: Neurotrophin receptors were initially identified in neural cells. They were recently detected in some cancers in association with invasiveness, but the function of these tyrosine kinase receptors was not previously investigated in colorectal cancer (CRC) cells. METHODS AND FINDINGS: We report herein that human CRC cell lines synthesize the neural growth factor Brain-derived neurotrophic factor (BDNF) under stress conditions (serum starvation). In parallel, CRC cells expressed high- (TrkB) and low-affinity (p75(NTR)) receptors at the plasma membrane, whereas TrkA and TrkC, two other high affinity receptors for NGF and NT-3, respectively, were undetectable. We demonstrate that BDNF induced cell proliferation and had an anti-apoptotic effect mediated through TrkB, as assessed by K252a, a Trk pharmacologic inhibitor. It suppressed both cell proliferation and survival of CRC cells that do not express TrkA nor TrkC. In parallel to the increase of BDNF secretion, sortilin, a protein acting as a neurotrophin transporter as well as a co-receptor for p75(NTR), was increased in the cytoplasm of primary and metastatic CRC cells, which suggests that sortilin could regulate neurotrophin transport in these cells. However, pro-BDNF, also detected in CRC cells, was co-expressed with p75(NTR) at the cell membrane and co-localized with sortilin. In contrast to BDNF, exogenous pro-BDNF induced CRC apoptosis, which suggests that a counterbalance mechanism is involved in the control of CRC cell survival, through sortilin as the co-receptor for p75(NTR), the high affinity receptor for pro-neurotrophins. Likewise, we show that BDNF and TrkB transcripts (and not p75(NTR)) are overexpressed in the patients' tumors by comparison with their adjacent normal tissues, notably in advanced stages of CRC. CONCLUSION: Taken together, these results highlight that BDNF and TrkB are essential for CRC cell growth and survival in vitro and in tumors. This autocrine loop could be of major importance to define new targeted therapies

Expression and pharmacological inhibition of TrkB and EGFR in glioblastoma

A member of the Trk family of neurotrophin receptors, tropomyosin receptor kinase B (TrkB, encoded by the NTRK2 gene) is an increasingly important target in various cancer types, including glioblastoma (GBM). EGFR is among the most frequently altered oncogenes in GBM, and EGFR inhibition has been tested as an experimental therapy. Functional interactions between EGFR and TrkB have been demonstrated. In the present study, we investigated the role of TrkB and EGFR, and their interactions, in GBM. Analyses of NTRK2 and EGFR gene expression from The Cancer Genome Atlas (TCGA) datasets showed an increase in NTRK2 expression in the proneural subtype of GBM, and a strong correlation between NTRK2 and EGFR expression in glioma CpG island methylator phenotype (G-CIMP+) samples. We showed that when TrkB and EGFR inhibitors were combined, the inhibitory effect on A172 human GBM cells was more pronounced than when either inhibitor was given alone. When U87MG GBM cells were xenografted into the flank of nude mice, tumor growth was delayed by treatment with TrkB and EGFR inhibitors, given alone or combined, only at specific time points. Intracranial GBM growth in mice was not significantly affected by drug treatments. Our findings indicate that correlations between NTRK2 and EGFR expression occur in specific GBM subgroups. Also, our results using cultured cells suggest for the first time the potential of combining TrkB and EGFR inhibition for the treatment of GBM

Copper uptake, accumulation and physiological changes in adult grapevines in response to excess copper in soil.

2014Publicada online em 24 de setembro

Use of phosphorus fertilization and mycorrhization as strategies for reducingcopper toxicity in young grapevines.

Established vineyard soils may have high copper (Cu) contents due to the ongoing foliar applications of copper-based fungicides. In viticulture, the replacement of old vineyards with new vines is common practice, however,limited by Cu excess in soil and its toxicity to young grapevines. The application of phosphorus (P) and ar-buscular mycorrhizal fungi (AMF) inoculation are potential strategies to reduce Cu toxicity to young grapevines.This study aimed to assess the effects of phosphorus fertilization and AMF (Rhizophagus clarus) inoculation ongrowth and physiological parameters of young grapevines grown in soil with high Cu content. The experimentwas conducted in a greenhouse, where natural grassland soil was artificially contaminated by the addition of60 mg kg−1Cu. The soils were treated with and without AMF inoculation, combined with additions of 0, 40 and100 mg P kg−1. After 90 days of cultivation, grapevine plants were assessed for chlorophyllafluorescence,photosynthetic pigment contents, superoxide dismutase (SOD) activity, plant height, plant biomass, and con-centrations of Cu and P in roots and shoots. Phosphorus fertilization promoted increases in seedling growth(related to the increase of total P concentration in roots and shoots), soluble Pi concentration in leaves, and thequantum yield of the PSII (YII) (associated with a reduction in shoot Cu concentration). The AMF inoculationincreased the concentration of P in roots and shoots, soluble Pi in leaves and electron transport rate (ETR).Phosphorus fertilization and inoculation of grapevines with AMF are strategies capable of reducing Cu toxicity inyoung grapevines.Made available in DSpace on 2020-01-09T00:39:35Z (GMT). No. of bitstreams: 1 1s2.0S0304423819300342main.pdf: 737187 bytes, checksum: e56f2e19f3c7c1c42fd8c46862c1afa4 (MD5) Previous issue date: 2019bitstream/item/208366/1/1-s2.0-S0304423819300342-main.pd