Increased expression of glucose transporters has been reported in many cancers. It is not known whether Sodium dependent GLucose Transporter 1 (SGLT1) is up-regulated in pancreatic cancer. We studied the expression of SGLT1, Bcl-2 and p53 in primary pancreatic adenocarcinomas related to survival. In primary tumors, mean SGLT1-Hscore (n = 83) was 4.24 (median 3.0, range 0.5-15.0). Patients with positive staining for Bcl-2 had higher mean SGLT1-Hscores than those without Bcl-2 expression: 5.87 vs. 3.07 (P = 0.025). No correlation was found between expression of p53 and SGLT1 (P = 0.881). On multivariate analysis TNM stage (P = 0.015) and SGLT1 (P = 0.030) showed prognostic value for disease free survival (DFS). For overall survival (OS), TNM stage (P<0.001) and chemotherapy (P = 0.048) were prognostic and SGLT1 showed a trend (P = 0.071). In a subgroup of younger patients (age < or = median, 63.9 y) who did not receive chemotherapy, SGLT1 was a very strong predictor of DFS (P = 0.005). We conclude that high SGLT1 expression (H score > median, 3.0) in pancreatic adenocarcinomas was significantly correlated with DFS and a trend was found for OS, especially in younger patients. High SGLT1 expression in primary tumors was correlated with high Bcl-2 expression, not with p53 expression. This supports our hypothesis that SGLT1 and Bcl-2 expression could serve as prognostic markers in pancreatic cancer.
Summary The root system is fundamental for plant development, is crucial for overall plant growth and is recently being recognized as the key for future crop productivity improvement. A major determinant of root system architecture is the initiation of lateral roots. While knowledge of the genetic and molecular mechanisms regulating lateral root initiation has mainly been achieved in the dicotyledonous plant Arabidopsis thaliana, only scarce data are available for major crop species, generally monocotyledonous plants. The existence of both similarities and differences at the morphological and anatomical level between plant species from both clades raises the question whether regulation of lateral root initiation may or may not be conserved through evolution. Here, we performed a targeted genome‐wide transcriptome analysis during lateral root initiation both in primary and in adventitious roots of Zea mays and found evidence for the existence of common transcriptional regulation. Further, based on a comparative analysis with Arabidopsis transcriptome data, a core of genes putatively conserved across angiosperms could be identified. Therefore, it is plausible that common regulatory mechanisms for lateral root initiation are at play in maize and Arabidopsis, a finding that might encourage the extrapolation of knowledge obtained in Arabidopsis to crop species at the level of root system architecture.
Abstract:Background & Aims: Alterations in signaling pathways that regulate resolution of
PURPOSE. Aging impairs corneal nerve density and sensitivity. Substance P (SP), a neuropeptide secreted by sensory nerves, regulates nerve morphology and nociception. Here, we investigate the relationship between aging, nerve morphology, and SP expression in mouse and human corneas. METHODS. SP levels in mouse corneas (wild type and substance P-knockout) and human corneas and tears were quantified with an ELISA assay. Corneal total nerve length (TNL) was measured with whole-mount b3-tubulin immunofluorescence in mouse and in vivo laser corneal confocal microscopy in humans. SP and b3-tubulin stained cross-sections were used to assess the colocalization of SP and nerves in human and mouse corneas. Ocular surface nociception was assessed with a wiping test in mice. RESULTS. SP colocalizes with sub-basal neurons in mice and humans. In WT mice, SP levels decrease with age (P ¼ 0.0045, 8 vs. 52 weeks; P ¼ 0.004, 26 vs. 52 weeks) as well as TNL (P ¼ 0.018, 8 vs. 26 weeks; P ¼ 0.0001, 8 vs. 52 weeks). Knockout mice show a greater TNL reduction (8 vs. 26 weeks, P ¼ 0.0016) than WT mice. In the oldest WT and age-matched KO mice, nociception is impaired (P ¼ 0.007 and P < 0.0001, respectively), and KO mice sensitivity is restored by topical SP treatment. In humans, SP levels are reduced in old subject corneas and correlate, in tears, with age (P ¼ 0.0368); TNL also decreases in older patients (P ¼ 0.0002). CONCLUSIONS. Age-associated corneal nerve loss is paralleled by reduction of SP expression in mice and humans. SP promotes the maintenance of normal nerve morphology in the long term and modulates nociception in the cornea.
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