125 research outputs found
Dbl oncogene expression in MCF-10 A epithelial cells disrupts mammary acinar architecture, induces EMT and angiogenic factor secretion.
The proteins of the Dbl family are guanine nucleotide exchange factors (GEFs) of Rho GTPases and are known to be involved in cell growth regulation. Alterations of the normal function of these proteins lead to pathological processes such as developmental disorders, neoplastic transformation, and tumor metastasis. We have previously demonstrated that expression of Dbl oncogene in lens epithelial cells modulates genes encoding proteins involved in epithelial-mesenchymal-transition (EMT) and induces angiogenesis in the lens. Our present study was undertaken to investigate the role of Dbl oncogene in epithelial cells transformation, providing new insights into carcinoma progression. To assess how Dbl oncogene can modulate EMT, cell migration, morphogenesis, and expression of pro-apoptotic and angiogenic factors we utilized bi- and three-dimensional cultures of MCF-10░A cells. We show that upon Dbl expression MCF-10░A cells undergo EMT. In addition, we found that Dbl overexpression sustain
Characterization of speech and language phenotype in GLUT1DS
Background: To analyze the oral motor, speech and language phenotype in a sample of pediatric patients with GLUT 1 transporter deficiency syndrome (GLUT1DS). Methods: eight Italian-speaking children with GLUT1DS (aged 4.6–15.4 years) in stable treatment with ketogenic diet from a variable time underwent a specific and standardized speech and language assessment battery. Results: All patients showed deficits with different degrees of impairment in multiple speech and language areas. In particular, orofacial praxis, parallel and total movements were the most impaired in the oromotor domain; in the speech domain patients obtained a poor performance in the diadochokinesis rate and in the repetition of words that resulted as severely deficient in seven out of eight patients; in the language domain the most affected abilities were semantic/phonological fluency and receptive grammar. Conclusions: GLUT1DS is associated to different levels of speech and language impairment, which should guide diagnostic and therapeutic intervention. Larger population data are needed to identify more precisely a speech and language profile in GLUT1DS patients
2C-B: A New Psychoactive Phenylethylamine Recently Discovered in Ecstasy Tablets Sold on the Swiss Black Market
This study sought to identify, by means of several analytical methods (GC-MS, HPLC-DAD, CE-DAD, FTIR, and NMR), 4-bromo-2,5-dimethoxyphenethylamine (2C-B), which was found in two sets of tablets obtained from the Swiss black market. Unequivocal identification of 2C-B was only achieved by a combination of mass spectrometric and NMR analysis. Quantitation of 2C-B was performed by HPLC-DAD and CE-DAD. The amounts of 2C-B found in the tablets (3-8 mg) were in the range of the minimum quantity required to induce the effects characteristic of this dru
Characterization of high- And low-risk hepatocellular adenomas by magnetic resonance imaging in an animal model of glycogen storage disease type 1A
Hepatocellular adenomas (HCAs) are benign tumors, of which the most serious complications are hemorrhage and malignant transformation to hepatocellular carcinoma (HCC). Among the various subtypes of HCA, the \u3b2-catenin-activated subtype (bHCA) is associated with greatest risk of malignant transformation. Magnetic resonance imaging (MRI) is an important tool to differentiate benign and malignant hepatic lesions, and preclinical experimental approaches may help to develop a method to identify MRI features associated with bHCA. HCAs are associated with various pathologies, including glycogen storage disease 1a (GSD1a). Here, we utilized a mouse model for GSD1a that develops HCA and HCC, and analyzed the mice in order to distinguish low-risk from high-risk tumors. Animals were scanned by MRI using a hepato-specific contrast agent. The mice were sacrificed after MRI and their lesions were classified using immunohistochemistry. We observed that 45% of the animals developed focal lesions, and MRI identified four different patterns after contrast administration: isointense, hyperintense and hypointense lesions, and lesions with peripheral contrast enhancement. After contrast administration, only bHCA and HCC were hypointense in T1-weighted imaging and mildly hyperintense in T2-weighted imaging. Thus, high-risk adenomas display MRI features clearly distinguishable from those exhibited by low-risk adenomas, indicating that MRI is a reliable method for early diagnosis and classification of HCA, necessary for correct patient management
A biology-driven approach identifies the hypoxia gene signature as a predictor of the outcome of neuroblastoma patients
A biology-driven approach identifies the hypoxia gene signature as a predictor of the outcome of neuroblastoma patients
Favorable prognostic role of tropomodulins in neuroblastoma
Neuroblastoma is a pediatric tumor of the sympatoadrenal lineage of the neural
crest characterized by high molecular and clinical heterogeneity, which are the main
causes of the poor response to standard multimodal therapy. The identification of new
and selective biomarkers is important to improve our knowledge on the mechanisms
of neuroblastoma progression and to find the targets for innovative cancer therapies.
This study identifies a positive correlation among tropomodulins (TMODs) proteins
expression and neuroblastoma progression. TMODs bind the pointed end of actin
filaments, regulate polymerization and depolymerization processes modifying actin
cytoskeletal dynamic and influencing neuronal development processes. Expression
levels of TMODs genes were analyzed in 17 datasets comprising different types
of tumors, including neuroblastoma, and it was demonstrated that high levels of
tropomodulin1 (TMOD1) and tropomodulin 2 (TMOD2) correlate positively with
high survival probability and with favorable clinical and molecular characteristics.
Functional studies on neuroblastoma cell lines, showed that TMOD1 knockin induced
cell cycle arrest, cell proliferation arrest and a mature functional differentiation.
TMOD1 overexpression was responsible for particular cell morphology and biochemical
changes which directed cells towards a neuronal favorable differentiation profile.
TMOD1 downregulation also induced cell proliferation arrest but caused the loss of
mature cell differentiation and promoted the development of neuroendocrine cellular
characteristics, delineating an aggressive and unfavorable tumor behavior. Overall,
these data indicated that TMODs are favorable prognostic biomarkers in neuroblastoma
and we believe that they could contribute to unravel a new pathophysiological
mechanism of neuroblastoma resistance contributing to the design of personalized
therapeutics opportunities
Hypoxia modulates the gene expression profile of immunoregulatory receptors in human mDCs: identification of TREM-1 as a novel hypoxic marker in vitro and in vivo.
2C-B: a new psychoactive phenylethylamine recently discovered in Ecstasy tablets sold on the Swiss black market.
This study sought to identify, by means of several analytical methods (GC-MS, HPLC-DAD, CE-DAD, FTIR, and NMR), 4-bromo-2,5-dimethoxyphenethylamine (2C-B), which was found in two sets of tablets obtained from the Swiss black market. Unequivocal identification of 2C-B was only achieved by a combination of mass spectrometric and NMR analysis. Quantitation of 2C-B was performed by HPLC-DAD and CE-DAD. The amounts of 2C-B found in the tablets (3-8 mg) were in the range of the minimum quantity required to induce the effects characteristic of this drug
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