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Trang P.,Yale University | Medina P.P.,Yale University | Wiggins J.F.,Mirna Therapeutics, Inc. | Ruffino L.,Mirna Therapeutics, Inc. | And 8 more authors.
Oncogene | Year: 2010

MicroRNAs (miRNAs) have recently emerged as an important new class of cellular regulators that control various cellular processes and are implicated in human diseases, including cancer. Here, we show that loss of let-7 function enhances lung tumor formation in vivo, strongly supporting the hypothesis that let-7 is a tumor suppressor. Moreover, we report that exogenous delivery of let-7 to established tumors in mouse models of non-small-cell lung cancer (NSCLC) significantly reduces the tumor burden. These results demonstrate the therapeutic potential of let-7 in NSCLC and point to miRNA replacement therapy as a promising approach in cancer treatment. © 2010 Macmillan Publishers Limited All rights reserved.

Yang N.,University of Wisconsin - Madison | Mosher R.,University of Wisconsin - Madison | Seo S.,University of Wisconsin - Madison | Beebe D.,University of Wisconsin - Madison | And 2 more authors.
American Journal of Pathology | Year: 2011

Stromal fibroblasts of breast carcinomas frequently express the cell surface proteoglycan syndecan-1 (Sdc1). In human breast carcinoma samples, stromal Sdc1 expression correlates with an organized, parallel, extracellular matrix (ECM) fiber architecture. To examine a possible link between stromal Sdc1 and the fiber architecture, we generated bioactive cell-free three-dimensional ECMs from cultures of Sdc1-positive and Sdc1-negative murine and human mammary fibroblasts (termed ECM-Sdc1 and ECM-mock, respectively). Indeed, ECM-Sdc1 showed a parallel fiber architecture that contrasted markedly with the random fiber arrangement of ECM-mock. When breast carcinoma cells were seeded into the fibroblast-free ECMs, ECM-Sdc1, but not ECM-mock, promoted their attachment, invasion, and directional movement. We further evaluated the contribution of the structural/compositional modifications in ECM-Sdc1 on carcinoma cell behavior. By microcontact printing of culture surfaces, we forced the Sdc1-negative fibroblasts to produce ECM with parallel fiber organization, mimicking the architecture observed in ECM-Sdc1. We found that the fiber topography governs carcinoma cell migration directionality. Conversely, an elevated fibronectin level in ECM-Sdc1 was responsible for the enhanced attachment of the breast carcinoma cells. These observations suggest that Sdc1 expression in breast carcinoma stromal fibroblasts promotes the assembly of an architecturally abnormal ECM that is permissive to breast carcinoma directional migration and invasion. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Mussap M.,Italian National Cancer Institute | Puxeddu E.,Puericulture Institute and Neonatal Section | Puddu M.,Puericulture Institute and Neonatal Section | Ottonello G.,Puericulture Institute and Neonatal Section | And 5 more authors.
Clinica Chimica Acta | Year: 2015

Neonatal sepsis still remains a major cause of morbidity and mortality in neonatal intensive care unit (NICU). Recently, soluble CD14 subtype (sDC14-ST) also named presepsin, was proposed as an effective biomarker for diagnosing, monitoring, and assessing the risk of neonatal sepsis and septic shock. The aim of this study was to investigate the diagnostic accuracy of sCD14-ST presepsin in diagnosing neonatal bacterial sepsis and in discriminating non-bacterial systemic inflammatory response syndrome (SIRS) from bacterial sepsis. This study involved 65 critically ill full-term and preterm newborns admitted to the neonatal intensive care unit (NICU), divided into three groups: 25 newborns with bacterial neonatal sepsis (group A); 15 newborns with a diagnosis of non-bacterial SIRS and with no localizing source of bacterial infection (group B); and 25 babies with no clinical or bacteriological signs of systemic or local infection receiving routine NICU care, most of them treated with phototherapy for neonatal jaundice (group C). A total of 102 whole blood samples were collected, 40 in group A, 30 in group B and 32 in group C. In 10 babies included in group A, sCD14-ST presepsin was also measured in an additional second blood sample collected 3. days after the start of antibiotic treatment. sCD14-ST presepsin was measured by a commercially available chemiluminescent enzyme immunoassay (CLEIA) optimized on an automated immunoassay analyzer. Statistical analysis was performed by means of MedCalc® statistical package; receiver operating characteristic (ROC) analysis was computed, and the area under the ROC curve (AUC) was used to evaluate the ability of sCD14-ST to discriminate neonatal bacterial sepsis from non-bacterial SIRS. Blood sCD14-ST presepsin levels were found significantly higher in bacterial sepsis when compared with controls (p < 0.0001); similarly, they were higher in non-bacterial SIRS when compared with controls (p < 0.0001). However, no statistically significant difference was found between bacterial sepsis and non-bacterial SIRS (p = 0.730). In our population, CRP and sCD14-ST did not correlate with each other. ROC analysis revealed that sCD14-ST presepsin has an area under the curve (AUC) of 0.995 (95% C.I.: 0.941-1.00) greater than that of CRP (0.827; 95% C.I.: 0.72-0.906). Similarly, in the group of babies with non-infectious SIRS, sCD14-ST AUC was greater than CRP AUC (0.979; 95% C.I.: 0.906-0.999 versus 0.771; 95% C.I.: 0.647-0.868). In controls, preliminary reference intervals for sCD14-ST ranged 223.4-599.7 ng/L, being significantly different from those previously published elsewhere. In conclusion, sCD14-ST presepsin could be introduced in clinical practice as a diagnostic tool for improving the management of neonatal sepsis and non-bacterial SIRS. © 2015 Elsevier B.V.

Jadus M.R.,Research Service VA Long Beach Healthcare System | Jadus M.R.,University of California at Irvine | Jadus M.R.,Laboratory Medicine Service | Natividad J.,Research Service VA Long Beach Healthcare System | And 10 more authors.
Clinical and Developmental Immunology | Year: 2012

Lung cancers remain one of the most common and deadly cancers in the world today (12.5 of newly diagnosed cancers) despite current advances in chemo- and radiation therapies. Often, by the time these tumors are diagnosed, they have already metastasized. These tumors demonstrate the classic hallmarks of cancer in that they have advanced defensive strategies allowing them to escape various standard oncological treatments. Immunotherapy is making inroads towards effectively treating other fatal cancers, such as melanoma, glioblastoma multiforme, and castrate-resistant prostate cancers. This paper will cover the escape mechanisms of bronchogenic lung cancer that must be overcome before they can be successfully treated. We also review the history of immunotherapy directed towards lung cancers. Copyright © 2012 Martin R. Jadus et al.

Carmignani L.,University of Milan | Picozzi S.,University of Milan | Spinelli M.,University of Milan | Di Pierro S.,University of Milan | And 6 more authors.
International Urology and Nephrology | Year: 2012

Purpose Despite the recent innovations, complications of prostate biopsy can occur. The aim of this study was a prospective monitoring of major septic complications occurring after transrectal prostate biopsy, to describe their causing agents, to report the clinical course of these patients, and to give guidelines based on our personal experience. Methods: This prospective study was carried out between January 2009 and September 2010. Complications were evaluated by telephone interviews. Results: Between January 2009 and September 2010, 447 (96.5%) completed the telephone interview. Urosepsis occurred in ten patients (2.2%) and in three cases evolved into septic shock. Of these ten patients, nine had a positive blood culture, of whom eight for Escherichia coli and one for Aeromonas hydrophila, Aeromonas caviae, and Aeromonas sobria. In seven cases, the E. coli isolated were resistant to fluoroquinolone and six produced an extended spectrum betalactamase. Six E. coli were classified as multidrugresistant organisms. Of the 10 patients, one died after the onset of multiorgan failure. For the other nine, the mean time spent in the hospital was 9 days (range, 6-15 days). Conclusions Escherichia coli are developing new drug resistances. Early recognition of patients who harbor MDRO E. coli in their rectum or in the urine could be an important strategy for preventing sepsis. If a patient who has recently undergone transrectal prostate biopsy shows clinical signs of sepsis in the 48 h, a multiresistant E. coli infection must be suspected. The patient must be admitted urgently to the hospital, and carbapenemantibiotic therapy should be started. © Springer Science+Business Media, B.V. 2012.

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