1,721,083 research outputs found
Histogram analysis of magnetic resonance images: evaluation of intra-tumoral heterogeneity and correlation with pathological findings in solid pancreatic tumors.
Full text linkObjectives To evaluate magnetic resonance (MR)-derived whole-tumor histogram analysis parameters in predicting aggressiveness of pancreatic ductal adenocarcinomas (PDACs) and neuroendocrine neoplasms (panNENs). Methods Pre-operative MR of 169 consecutive patients with PDAC or panNEN were retrospectively analyzed. T1-/T2-weighted images and apparent diffusion coefficient (ADC) maps were analyzed. Histogram-derived parameters were compared to several pathological features (grade, vascular infiltration, nodal and hepatic metastases) using Mann-Whitney U test. Diagnostic accuracy was assessed by receiver operating characteristic area under curve (ROC-AUC) analysis; sensitivity and specificity were assessed for each histogram parameter. Results No significant differences were found among histogram parameters for prediction of PDACs grade. ADCentropy was significantly higher in G2-3 panNENs with ROC-AUC 0.757; sensitivity was 83.3%. ADCentropy was significantly higher in PDACs with vascular involvement (p=.022; AUC=.641), with specificity of 92.2%. ADCskewness was significantly higher in PDACs with nodal metastases (p=.027; AUC=.642), with 72% specificity. ADCkurtosis was higher in panNENs with vascular involvement, nodal and hepatic metastases (p= .008, .021, and .008; ROC-AUC= 0.820, 0.709, and 0.820); sensitivity and specificity were: 85.7/74.3%; 36.8/96.5%; and 100/62.8%. No significant differences between groups were found for other histogram-derived parameters (p >.05). Conclusions Whole-tumors histogram analysis of ADC values is a valuable tool for predicting aggressiveness of PDACs and panNENs. Our results indicate that histogram metrics related to intra-tumor heterogeneity, as ADCentropy, ADCkurtosis and ADCskewness are the most accurate parameters for the identification of PDACs and panNENs with higher biological aggressiveness. Further and larger studies are needed to incorporate the results of the histogram analysis within decision support models and to mine these data to detect possible correlations with genomic patterns
Pemigatinib, a potent inhibitor of FGFRs for the treatment of cholangiocarcinoma
No full textThe prognosis of patients affected by cholangiocarcinoma is classically poor. Until recently, chemotherapeutic drugs were the only systemic treatment option available, leading to an overall survival lower than 1 year. In recent decades, different genetic alterations have been identified as playing a key role in the oncogenic signaling. A subgroup of intrahepatic cholangiocarcinoma is characterized byFGFRfamily mutations, more frequently represented by gene fusions ofFGFR2. Based on the results of FIGHT-202 trial, in April 2020 the US FDA approved the FGFR inhibitor pemigatinib in advanced previously treated cholangiocarcinoma patients withFGFR2rearrangements, opening the way to targeted therapy in this disease. This review summarizes the body of evidence about the efficacy of pemigatinib in cholangiocarcinoma.Lay abstract Cholangiocarcinoma is cancer that forms in the slender tubes bile ducts that carry the digestive fluid bile. This condition, also known as bile duct cancer, is a type of tumor that is very difficult to treat with common chemotherapy. Intrahepatic cholangiocarcinoma, those tumors occurring in the parts of the bile ducts within the liver, are frequently caused by alterations of a gene calledFGFR2. Pemigatinib is a novel potent drug that selectively inhibits the function of altered FGFR2 and recently demonstrated to be a valid treatment for patients affected by intrahepatic cholangiocarcinoma. Here, we present results about the efficacy of pemigatinib in this disease
Novel sol-gel organic-inorganic hybrid materials for drug delivery
No full textPurpose: The aim of the present study was to synthetize and characterize novel sol-gel organic-inorganic hybrid materials to be used for controlled drug delivery application. Materials and Methods: Organic-inorganic hybrid class I materials based on poly(ε-caprolactone) (PCL 6, 12, 24 and 50 wt%) and zirconia-yttria (ZrO2-5%Y2O3) were synthesized by a sol-gel method, from a multicomponent solution containing zirconium propoxide [Zr(OC2H7)4], yttrium chloride (YCl3), PCL, water and chloroform (CHCl3). The structure of the hybrids was obtained by means of hydrogen bonds between the Zr-OH group (H-donor) in the sol-gel intermediate species and the carboxylic group (H-acceptor) in the repeating units of the polymer. Results: The presence of hydrogen bonds between organic-inorganic components of the hybrid materials was suggested by Fourier transform infrared (FTIR) analysis, and strongly supported by solid-state NMR. A single-step, sol-gel process was then used to precipitate microspheres containing ketoprofen or indomethacin for controlled drug delivery applications. Release kinetics in a simulated body fluid (SBF) were subsequently investigated. The amount of drug released was detected by UV-VIS spectroscopy. Pure anti-inflammatory agents exhibited linear release with time, in contrast drugs entrapped in the organic-inorganic hybrids were released with a logarithmic time dependence, starting with an initial burst effect followed by a gradual decrease. Conclusions: The synthesis of amorphous materials containing drugs, obtained by sol-gel methods, helps to devise new strategies for controlled drug delivery system desig
Characterization,bioactivity and ampicillin release kinetics of of TiO2 and TiO2-4SiO2 synthesized by sol-gel processing
No full textLocal drug delivery of antimicrobics by sustained release delivery system can be used to treat periodontal disease. Advantages of these systems may include maintaining high levels of antibiotic in the gingival crevicular fluid for a sustained period of time and ease of use with high patient acceptance. The materials used are TiO2 and TiO24SiO2, mixed with sodium ampicillin, a broad-spectrum antibiotic, have been synthesized by sol-gel method. The amorphous nature of the gels was ascertained by X-ray diffraction analysis. Release kinetics in a simulated body fluid (SBF) have been subsequently investigated. The amount of sodium ampicillin released has been detected by UV-VIS spectroscopy and SEM. The release kinetics seems to occur in more than one stage. HPLC analysis has also been taken to ensure the integrity of ampicillin after the synthetic treatment. Finally, SEM micrographs and EDS analysis showed the formation of a hydroxyapatite layer on the surface of the samples soaked in SBF. Both the materials showed good release and could be used as drug delivery bioactive systems. High antimicrobial effects of samples against Escherichia coliand Streptococcus mutants were foun
HOX Genes Family and Cancer: A Novel Role for Homeobox B9 in the Resistance to Anti-Angiogenic Therapies
No full textSimple SummaryThe inhibition of angiogenesis, relying on the use of drugs targeting the VEGF signaling pathway, has become one of the main strategies for cancer treatment. However, the intrinsic and acquired resistance to this type of therapy limit its efficacy. Thus, the identification of novel therapeutic targets is urgently needed. The resistance to anti-angiogenic treatment often occurs through the activation of alternative VEGF independent signaling pathways and recruitment of bone marrow-derived pro-angiogenic cells in the tumor microenvironment. HOX genes are key regulators of embryonic development, also involved in angiogenesis and in cancer progression. HOXB9 upregulation occurs in many types of cancer and it has been identified as a critical transcription factor involved in tumour resistance to anti-angiogenic drugs. Indeed, HOXB9 modulates the expression of alternative pro-angiogenic secreted factors in the tumour microenvironment leading tumor escape from the anti-angiogenic treatments. Hence, HOXB9 could serves as a novel therapeutic target to overcome the resistance to anti-angiogenic therapies.Angiogenesis is one of the hallmarks of cancer, and the inhibition of pro-angiogenic factors and or their receptors has become a primary strategy for cancer therapy. However, despite promising results in preclinical studies, the majority of patients either do not respond to these treatments or, after an initial period of response, they develop resistance to anti-angiogenic agents. Thus, the identification of a novel therapeutic target is urgently needed. Multiple mechanisms of resistance to anti-angiogenic therapy have been identified, including the upregulation of alternative angiogenic pathways and the recruitment of pro-angiogenic myeloid cells in the tumor microenvironment. Homeobox containing (HOX) genes are master regulators of embryonic development playing a pivotal role during both embryonic vasculogenesis and pathological angiogenesis in adults. The importance of HOX genes during cancer progression has been reported in many studies. In this review we will give a brief description of the HOX genes and their involvement in angiogenesis and cancer, with particular emphasis on HOXB9 as a possible novel target for anti-angiogenic therapy. HOXB9 upregulation has been reported in many types of cancers and it has been identified as a critical transcription factor involved in resistance to anti-angiogenic drugs
Galactosylated dopamine enters into the brain, blocks the mesocorticolimbic system and modulates activity and scanning time in Naples high excitability rats.
No full textNeuroscience. 2008 Mar 3;152(1):234-44.
Galactosylated dopamine enters into the brain, blocks the mesocorticolimbic
system and modulates activity and scanning time in Naples high excitability rats.
Ruocco LA, Viggiano D, Viggiano A, Abignente E, Rimoli MG, Melisi D, Curcio A,
Nieddu M, Boatto G, Carboni E, Gironi Carnevale UA, Sadile AG.
Department of Experimental Medicine, Faculty of Medicine, II University of
Naples, Naples, Italy.
Pathological conditions, such as Parkinson's disease and attention deficit
hyperactivity disorder, have been linked to alterations of specific dopamine (DA)
pathways. However, since exogenous DA does not cross the blood-brain barrier, DA
levels can be modulated e.g. by DA precursors or DA reuptake blockers. Hereby
histochemical, analytical and behavioral evidence shows that a galactosylated
form of DA (GAL-DA) carries DA into the brain, thus modulating activity and
nonselective attention in rats. To this aim adult male rats of the Naples
high-excitability (NHE) and random bred controls (NRB) lines were given a single
i.p. injection of GAL-DA (10 or 100 mg/kg). Three hours later the behavior was
videotaped and analyzed for horizontal activity, orienting frequency and scanning
duration. The dose of 100 mglkg of GAL-DA reduced by 25% the horizontal activity
in NHE rats, mainly in the first part of the testing period. No effect was
observed on orienting frequency or on scanning duration. However, GAL-DA 100
mg/kg was associated with longer rearing episodes in the second part of the
testing period in NHE rats. In parallel experiments histochemistry with a
galactose-specific lectin showed 10% increase in galactose residues into the
striatum between 0.5 and 3.0 h. To quantify the level of GAL-DA, its metabolite
DA-succinate and DA in the prefrontal cortex, neostriatum, and cerebellum, rats
were killed 2.0 h after the injection of prodrug. Mass high performance liquid
chromatography (HPLC) was used for analysis of GAL-DA and DA succinate whereas
electrochemical HPLC for DA. Both HPLC techniques demonstrate that GAL-DA carries
and releases DA into the brain. Specifically 100 mg/kg of GAL-DA increased DA
level in the striatum in the NHE rats only. Moreover, DA in the mesencephalon
(MES) was correlated positively with striatal and prefrontal cortex DA in NHE
rats. In contrast DA in the MES was negatively correlated with striatal DA in
NRB. GAL-DA disrupted these correlations in both rat lines. Thus, this new DA
prodrug may modify DA neurotransmission and might have a potential clinical
application.
PMID: 18164552 [PubMed - indexed for MEDLINE
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Role of molecular genetics in the clinical management of cholangiocarcinoma
No full textThe incidence of cholangiocarcinoma (CCA) has steadily increased during the past 20 years, and mortality is increasing. The majority of patients with CCA have advanced or metastatic disease at diagnosis, and treatment options for unresectable disease are limited, resulting in poor prognosis. However, recent identification of targetable genomic alterations has expanded treatment options for eligible patients. Given the importance of early and accurate diagnosis in optimizing patient outcomes, this review discusses best practices in CCA diagnosis, with a focus on categorizing molecular genetics and available targeted therapies. Imaging and staging of CCAs are discussed, as well as recommended biopsy collection techniques, and molecular and genomic profiling methodologies, which have become increasingly important as molecular biomarker data accumulate. Approved agents targeting actionable genomic alterations specifically in patients with CCA include ivosidenib for tumors harboring IDH1 mutations, and infigratinib and pemigatinib for those with FGFR2 fusions. Other agents currently under development in this indication have shown promising results, which are presented here
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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