169,754 research outputs found
Hedgehog driven regulatory network sustains chemoresistance and mesenchymal phenotype in Colorectal Cancer cells
No full textTitle: Hedgehog driven regulatory network sustains chemoresistance and mesenchymal
phenotype in Colorectal Cancer cells.
Authors: A. Citarella, G. Catanzaro, S. ZM Besharat, F. Barbagallo, S. Trocchianesi, C. Sabato, T.
M. Autilio, A. Asquino, A. Vacca, M. Venneri, E. Ferretti, A. Po.
Background: Colorectal cancer (CRC) is a leading cause of mortality and morbidity. CRC is
characterized by frequent development of chemoresistance, achieved by the modulation of
signaling pathways that regulate cell survival. Thus, understanding mechanisms related to
aggressive features remains one of the most important goal for the development of more
efficient strategies.
The deregulation of different oncogenic pathways is involved in the acquisition of aggressive
features and chemoresistance. In this context of CRC, we previously showed that the Hedgehog
pathway regulates chemoresistance by up-regulating ABC transporters. Together with HH
another important pathway involved in stemness features of normal colonic mucosa and is
Notch1 pathway.
Recent studies highlight the crosstalk between Notch1 and HH-GLI1 signaling is fundamental in
different development contexts.
The aim of our work was to investigate the role of Hedgehog-GLI1 together with Notch1
pathway in CRC resistance to chemotherapy.
Methods: We performed our experiments in different cellular models derived from two CRC
HT29 and HCT116 cell lines. Cells cultured in 2D and 3D (organoids) conditions were treated
with 5-Fluoruracil, Notch1 inhibitor (DAPT), and HH-GLI1 inhibitor (GANT-61) and Arsenic
Trioxide (ATO) inhibitor of both pathways. Proteins and RNA levels were evaluated.
Results: First, we found that HT29 cells (BRAF mut) and HCT116 (KRAS mut) expressed Notch1
and GLI1 and that the HH and Notch1 inhibitors were able to downregulate the signaling but
were not able to induce apoptosis, while the combinatory treatments induce apoptosis.
Moreover, the inhibition of HH-GLI1 and Notch1 was able to induce chemosensitivity to 5-
Fluoruracil, by increasing cell death.
The combined inhibition of HH and Notch1 together with 5fu treatment induces differentiation
markers axin, e-cadherin and klf4.
In organoids we observed that the combined inhibition of HH-GLI1 and Notch1 together with 5-
Fu impaired the protein expression of the Epithelial to Mesenchymal Transition (EMT) marker
Vimentin.
CONCLUSIONS Our data highlight the role of HH- GLI1 pathway together with Notch1 signaling
in regulating cell death differentiation and mesenchymal phenotype in CRC cellular models
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Personalized Medicine for the Management of RDS in Preterm Neonates
No full textContinuous positive airway pressure and surfactant represent the first- and second-line treatment for respiratory distress syndrome in preterm neonates, as European and American guidelines, since 2013 and 2014, respectively, started to recommend surfactant replacement only when continuous positive airway pressure fails. These recommendations, however, are not personalized to the individual physiopathology. Simple clinical algorithms may have improved the diffusion of neonatal care, but complex medical issues can hardly be addressed with simple solutions. The treatment of respiratory distress syndrome is a complex matter and can be only optimized with personalization. We performed a review of tools to individualize the management of respiratory distress syndrome based on physiopathology and actual patients' need, according to precision medicine principles. Advanced oxygenation metrics, lung ultrasound, electrical impedance tomography, and both quantitative and qualitative surfactant assays were examined. When these techniques were investigated with diagnostic accuracy studies, reliability measures have been meta-analysed. Amongst all these tools, quantitative lung ultrasound seems the more developed for the widespread use and has a higher diagnostic accuracy (meta-analytical AUC = 0.952 [95% CI: 0.951-0.953]). Surfactant adsorption (AUC = 0.840 [95% CI: 0.824-0.856]) and stable microbubble test (AUC = 0.800 [95% CI: 0.788-0.812]) also have good reliability, but need further industrial development. We advocate for a more accurate characterization and a personalized approach of respiratory distress syndrome. With the above-described currently available tools, it should be possible to personalize the treatment of respiratory distress syndrome according to physiopathol-ogy
Absolute quantitative PCR for detection of molecular biomarkers in melanoma patients: a preliminary report
No full textMalignant melanoma is the most malignant tumours of skin and mucous membranes mainly due to its aggressive biological behaviour and tendency to generate early metastases. Unfortunately, the mechanisms underlying the development, progression and the expression of an aggressive melanoma phenotype still remain largely unknown
Mitomycin C in highly myopic eyes - Author reply
No full textOphthalmology. 2005 Feb;112(2):208-18; discussion 219.
Mitomycin C modulation of corneal wound healing after photorefractive keratectomy in highly myopic eyes.
Gambato C, Ghirlando A, Moretto E, Busato F, Midena E.
SourceRefractive Surgery Service and Antimetabolite Therapy Research Unit, Department of Ophthalmology, University of Padova, Padova, Italy.
Abstract
PURPOSE: To evaluate the role of topical mitomycin C in corneal wound healing (CWH) after photorefractive keratectomy (PRK) in highly myopic eyes.
DESIGN: Prospective, double-masked, randomized clinical trial.
PARTICIPANTS: Seventy-two eyes of 36 patients affected by high (>7 diopters) myopia.
METHODS: In each patient, one eye was randomly assigned to PRK with intraoperative topical 0.02% mitomycin C application, and the fellow eye was treated with a placebo. Postoperatively, mitomycin C-treated eyes received artificial tears (3 times daily, tapered in 3 months), whereas the fellow eye was treated with fluorometholone sodium 2% and artificial tears (3 times daily, tapered in 3 months).
MAIN OUTCOME MEASURES: Uncorrected visual acuity (UCVA) and best-corrected visual acuity (BCVA), contrast sensitivity, manifest refraction, and biomicroscopy. Contrast sensitivity was determined using the Pelli-Robson chart. Corneal confocal microscopy documented CWH.
RESULTS: Mean follow-up was 18 months (range, 12-36). No side effects or toxic effects were documented. At 12-month follow-up examination, UCVAs (logarithm of the minimum angle of resolution) were 0.4+/-0.48 and 0.5+/-0.53 (P = .03) in mitomycin C-treated eyes and corticosteroid-treated eyes, respectively. At 1 year, corneal haze developed in 20% of corticosteroid-treated eyes, versus 0% of mitomycin C-treated eyes. At 12, 24, and 36 months, corneal confocal microscopy showed activated keratocytes and extracellular matrix significantly more evident in untreated eyes (Ps = 0.004, 0.024, and 0.046, respectively).
CONCLUSION: Topical intraoperative application of 0.02% mitomycin C can reduce haze formation in highly myopic eyes undergoing PRK.
Comment in
Ophthalmology. 2006 Feb;113(2):357; author reply 357-8
Circulating tumor cell-related transcripts in blood as prognostic biomarkers of early recurrence after liver resection for colorectal metastases
No full textSeveral prognostic factors were proposed to improve early detection of recurrence after liver resection of metastases of colorectal cancer. Circulating tumor cell-related transcripts were evaluated in colorectal cancer patients with conflicting results. The aim of this study was to investigate usefulness of carcinoembryonic antigen CAM5, epidermal growth factor receptor, and ERCC1 transcripts in the bloodstream as predictive factors of recurrence in patients who underwent liver resection for metastases of colorectal cancer
PAX3d mRNA over 2.76 copies/mu L in the bloodstream predicts cutaneous malignant melanoma relapse
No full textObjective: The aim of this study was to evaluate if our molecular algorithm, based on tumor circulating transcripts, may predict relapse risk in cutaneous malignant melanoma (CMM).
Results: The multi-marker panel was able to differentiate patients with CMM from HC with high diagnostic sensitivity and specificity, especially for MITF-m and TGFB2 (91-100%) whose levels decreased during follow-up of recurrence-free patients, and remained stable in the case of relapse. PAX3d higher than 2.76 copies/mu L emerged as a promising biomarker [specificity = 75-93% and negative predictive value = 75-98%] to stratify subjects at high risk of CMM recurrence independently of age, gender and AJCC staging [OD = 9.5(3.2-28.0), p<0.001]. The survival analysis confirmed PAX3d performance in relapse prediction with significant differences in recurrence risk 12 months after the basal time-point (p = 0.008).
Materials and Methods: Peripheral blood was collected from 111 CMM patients and from 87 healthy controls ( HC) randomly selected. Each specimen was examined by qRT-PCR analysis for the expression of 3 tumor-related transcripts (PAX3d, MITF-m and TGFB2) at diagnosis, and at the following 6 and 12 months during clinical monitoring.
Conclusions: We demonstrated the usefulness of our molecular algorithm to indirectly detect circulating melanoma cells in blood, along with PAX3d capability to assess patients' progression and relapse prediction
Dispelling the Myths Behind First-author Citation Counts
No full textWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
A Multi-Language Comparison of Influences on Author Verification using Character N-Grams
No full textWe create a new multi-language corpus for author verification based on Wikipedia talkpages, and evaluate the influence that differences in topic and time have on character n-gram author profiles. Topic alignment between two texts is found to increase author verification precision, and an authors writing style is found to change over time, but not more significantly after 3 years than after 1 year.Information ArchitectureWISElectrical Engineering, Mathematics and Computer Scienc
A 0.12mm<sup>2</sup> Wien-Bridge Temperature Sensor with 0.1°C (3σ) Inaccuracy from -40°C to 180°C
No full text Resistor-based temperature sensors can achieve much higher resolution and energy efficiency than conventional BJT-based sensors [1], but they typically occupy more area (> 0.25 mm 2 ) and have lower operating temperatures (le 125 {circ} {C}) [2]-[4]. This work describes a 0.12mm 2 resistor-based sensor that uses a Wien-bridge (WB) filter to achieve 0.1 {circ} {C} (3 sigma) inaccuracy from - 40 {circ} {C} to 180 {circ} {C}. Compared to a state-of-the-art WB sensor [4], it occupies 6 × less area and achieves comparable relative accuracy over a 76% wider operating range. Session 10.3 Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Electronic InstrumentationMicroelectronic
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