Proteomics identifies ubiquitin-proteasome targets and new roles for chromatin-remodeling in the Arabidopsis response to phosphate starvation.

In order to identify new regulators of the phosphate (Pi) starvation signaling pathway in plants, we analyzed variation in the abundance of nuclear-enriched proteins isolated from Arabidopsis roots that depends on Pi supply. We used 2-D fluorescence difference gel electrophoresis and MALDI-TOF/TOF techniques for proteome separation, visualization and relative protein abundance quantification and identification. Pi-controlled proteins identified in our analysis included components of the chromatin remodeling, DNA replication, and mRNA splicing machineries. In addition, by combining Pi starvation conditions with proteasome inhibitor treatments, we characterized the role of the ubiquitin-proteasome system, a major mechanism for targeted protein degradation in eukaryotes, in the control of the stability of Pi-responsive proteins. Among Pi-responsive proteins, the histone chaperone NAP1;2 was selected for further characterization, and was shown to display differential nucleo-cytoplasmic accumulation in response to Pi deprivation. We also found that mutants affecting three members of the NAP1 family accumulate lower Pi levels and display reduced expression of Pi starvation-inducible genes, reflecting a potential regulatory role for these chromatin-remodeling proteins in Pi homeostasis. BIOLOGICAL SIGNIFICANCE: In this study, we explore the feasibility of nuclear proteomics to identify regulatory proteins and ubiquitin-proteasome targets within a specific stress signaling pathway in plants, in our case phosphate starvation signaling in Arabidopsis. It will be of interest for researchers involved in the dissection of any signaling pathway in plants, in particular those with an interest in the ubiquitin-proteasome functions, and for the plant nutrition community.

PDGFRα/ß and VEGFR2 polymorphisms in colorectal cancer: incidence and implications in clinical outcome.

BACKGROUND: Angiogenesis plays an essential role in tumor growth and metastasis, and is a major target in cancer therapy. VEGFR and PDGFR are key players involved in this process. The purpose of this study was to assess the incidence of genetic variants in these receptors and its potential clinical implications in colorectal cancer (CRC). METHODS: VEGFR2, PDGFRα and PDGFRß mutations were evaluated by sequencing their tyrosine kinase domains in 8 CRC cell lines and in 92 samples of patients with CRC. Correlations with clinicopathological features and survival were analyzed. RESULTS: Four SNPs were identified, three in PDGFRα [exon 12 (A12): c.1701A>G; exon 13 (A13): c.1809G>A; and exon 17 (A17): c.2439+58C>A] and one in PDGFRß [exon 19 (B19): c.2601A>G]. SNP B19, identified in 58% of tumor samples and in 4 cell lines (LS174T, LS180, SW48, COLO205), was associated with higher PDGFR and pPDGFR protein levels. Consistent with this observation, 5-year survival was greater for patients with PDGFR B19 wild type tumors (AA) than for those harboring the G-allele genotype (GA or GG) (51% vs 17%; p=0.073). Multivariate analysis confirmed SNP B19 (p=0.029) was a significant prognostic factor for survival, independent of age (p=0.060) or TNM stage (p<0.001). CONCLUSIONS: PDGFRß exon 19 c.2601A>G SNP is commonly encountered in CRC patients and is associated with increased pathway activation and poorer survival. Implications regarding its potential influence in response to PDGFR-targeted agents remain to be elucidated.

Efectos del ácido ursodeoxicólico en pacientes con colestasis gravídica / Effects of ursodeoxycholic acid in patients with cholestasis of pregnancy

In an open, pilot study, the efficancy and safety of ursodeoxycholic acid (UDCA) in the treatment of intrahepatic cholestasis of pregnancy was investigated. four patients received 1 g/ñday of UDCA during 20 days and another 2 patients received identical periods of treatment separated by a 14-day interval free of drug. Pruritus and serum levels of toal bile salts and glutamic-pyruvic transaminase improved significantly during treatment with UDCA. Although pruritus and the laboratory alterations had a relapse in the second week after UDCA was discontinued, they improved again in the patients who received a second treatment with UDCA. No adverse reactions were detected in the mothers or in their babies. All neuborns are thriving normally, in a follow-up lasted 3 to 6 months after delivery. It is concluded that UDCA appears to be safe when administered in late pregnancy; its primising efficacy in the treatment of intrahepatic cholestasis of pregnancy should now be confirmed in controlled clinical trials

Cáncer de ovario: comunicación preliminar / Ovarian cancer: preliminary communication

Se analizan los antecedentes clínicos de 51 pacientes con cáncer de ovario, estudiadas y tratadas en el Servicio de Obstetricia y Ginecología del Hospital del Salvador, entre diciembre de 1980 y diciembre de 1986. El diagnóstico se efectuó en etapas avanzadas en 68,2% de los casos, siendo los tumores de origen epitelial la variedad predominante, en el 78,3%. Se desarrolló un protocolo operatorio preestablecido en forma completa en el 82,3%, y se analizan las principales complicaciones postoperatorias. La terapia complementaria predominante fue quimioterapia, que se efectuó en 23 de 27 casos. La tasa de mortalidad en el tiempo de seguimiento alcanza al 8,3% en etapa I; 25% en etapa II; 35% en etapa III, y 70% en etapa IV. En 12 pacientes se ha efectuado revisión de "segundo vistazo", evidenciándose ausencia de enfermedad en sólo la mitad de los casos