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221.
Rachel A. Kudgus Annamaria Szabolcs Jameel Ahmad Khan Chad A. Walden Joel M. Reid J. David Robertson Resham Bhattacharya Priyabrata Mukherjee 《PloS one》2013,8(3)
Background
Pancreatic cancer is one of the deadliest of all human malignancies with limited options for therapy. Here, we report the development of an optimized targeted drug delivery system to inhibit advanced stage pancreatic tumor growth in an orthotopic mouse model.Method/Principal Findings
Targeting specificity in vitro was confirmed by preincubation of the pancreatic cancer cells with C225 as well as Nitrobenzylthioinosine (NBMPR - nucleoside transporter (NT) inhibitor). Upon nanoconjugation functional activity of gemcitabine was retained as tested using a thymidine incorporation assay. Significant stability of the nanoconjugates was maintained, with only 12% release of gemcitabine over a 24-hour period in mouse plasma. Finally, an in vivo study demonstrated the inhibition of tumor growth through targeted delivery of a low dose of gemcitabine in an orthotopic model of pancreatic cancer, mimicking an advanced stage of the disease.Conclusion
We demonstrated in this study that the gold nanoparticle-based therapeutic containing gemcitabine inhibited tumor growth in an advanced stage of the disease in an orthotopic model of pancreatic cancer. Future work would focus on understanding the pharmacokinetics and combining active targeting with passive targeting to further improve the therapeutic efficacy and increase survival. 相似文献222.
Daniela Rossi Alice Pedrali Annamaria Marra Luca Pignataro Dirk Schepmann Bernhard Wünsch Lian Ye Kristina Leuner Marco Peviani Daniela Curti Ornella Azzolina Simona Collina 《Chirality》2013,25(11):814-822
In this study we addressed the role of chirality in the biological activity of RC-33 , recently studied by us in its racemic form. An asymmetric synthesis procedure was the first experiment, leading to the desired enantioenriched RC-33 but with an enantiomeric excess (ee) not good enough for supporting the in vitro investigation. An enantioselective high‐performance liquid chromatography (HPLC) procedure was then successfully carried out, yielding both RC-33 enantiomers in amounts and optical purity suitable for the pharmacological study. The absolute configuration of pure enantiomers was easily assigned exploiting the asymmetric synthesis previously devised. As emerged in the preliminary in vitro biological investigation, (S)‐ and (R)-RC-33 possess a comparable affinity towards the σ1 receptor and a very a similar behavior in the calcium influx assay, resulting in an equally effective σ1 receptor agonist. Overall, the results obtained so far suggest that the interaction with the biological target is nonstereoselective and leads us to hypothesize that there is a lack of stereoselectivity in the biological activity of RC-33 . Chirality 25:814–822, 2013. © 2013 Wiley Periodicals, Inc. 相似文献
223.
Annamaria MorelliLinda Vignozzi Mario MaggiLuciano Adorini 《生物化学与生物物理学报:疾病的分子基础》2011,1812(8):859-866
The metabolic syndrome (MetS) is an insulin-resistant state characterized by a cluster of cardiovascular risk factors, including abdominal obesity, hyperglycemia, elevated blood pressure and combined dyslipidemia. In this review, we discuss the potential of farnesoid X receptor (FXR) agonists in the treatment of erectile dysfunction (ED), a multifactorial disorder often comorbid with MetS. FXR not only regulates lipid and glucose homeostasis but also influences endothelial function and atherosclerosis, suggesting a regulatory role for this hormone nuclear receptor in the cardiovascular complications associated with the MetS, including ED. MetS induces ED via several mechanisms, and in particular through endothelial dysfunction in penile vessels. In a high-fat diet rabbit model of MetS, a 3-month treatment with the potent and selective FXR agonist INT-747 restores endothelium-dependent relaxation in isolated cavernous tissue, normalizing responsiveness to acetylcholine and to electrical field stimulation. Accordingly, eNOS expression in the penis is greatly up-regulated by INT-747 treatment. Experiments in a rat model of chemically-induced type 1 diabetes further demonstrate that INT-747 treatment preserves erectile function induced by electrical stimulation of the cavernous nerve. These results add a new facet to the pleiotropic activities mediated by FXR, and reveal novel beneficial effects of FXR activation with potential clinical relevance. This article is part of a Special Issue entitled: Translating nuclear receptors from health to disease. 相似文献
224.
Valerio Pazienza Annamaria la Torre Filomena Baorda Michela Alfarano Massimiliano Chetta Lucia Anna Muscarella Claudia Battista Massimiliano Copetti Dieter Kotzot Klaus Kapelari Dalia Al-Abdulrazzaq Kusiel Perlman Etienne Sochett David E. C. Cole Fabio Pellegrini Lucie Canaff Geoffrey N. Hendy Leonardo D’Agruma Leopoldo Zelante Massimo Carella Alfredo Scillitani Vito Guarnieri 《PloS one》2013,8(12)
Hyperparathyroidism Jaw-Tumour Syndrome (HPT-JT) is characterized by primary hyperparathyroidism (PHPT), maxillary/mandible ossifying fibromas and by parathyroid carcinoma in 15% of cases. Inactivating mutations of the tumour suppressor CDC73/HRPT2 gene have been found in HPT-JT patients and also as genetic determinants of sporadic parathyroid carcinoma/atypical adenomas and, rarely, typical adenomas, in familial PHPT. Here we report the genetic and molecular analysis of the CDC73/HRPT2 gene in three patients affected by PHPT due to atypical and typical parathyroid adenomas, in one case belonging to familial PHPT. Flag-tagged WT and mutant CDC73/HRPT2 proteins were transiently transfected in HEK293 cells and functional assays were performed in order to investigate the effect of the variants on the whole protein expression, nuclear localization and cell overgrowth induction. We identified four CDC73/HRPT2 gene mutations, three germline (c.679_680delAG, p.Val85_Val86del and p.Glu81_Pro84del), one somatic (p.Arg77Pro). In three cases the mutation was located within the Nucleolar Localisation Signals (NoLS). The three NoLS variants led to instability either of the corresponding mutated protein or mRNA or both. When transfected in HEK293 cells, NoLS mutated proteins mislocalized with a predeliction for cytoplasmic or nucleo-cytoplasmic localization and, finally, they resulted in overgrowth, consistent with a dominant negative interfering effect in the presence of the endogenous protein. 相似文献
225.
Chiocchetti R Grandis A Bombardi C Lucchi ML Dal Lago DT Bortolami R Furness JB 《Cell and tissue research》2006,323(2):183-196
To investigate extrinsic origins of calcitonin gene-related peptide immunoreactive (CGRP-IR) nerve fibres in the sheep ileum,
the retrograde fluorescent tracer Fast Blue (FB) was injected into the ileum wall. Sections of thoraco-lumbar dorsal root
ganglia (DRG) and distal (nodose) vagal ganglia showing FB-labelled neurons were processed for CGRP immunohistochemistry.
The distribution of CGRP-IR in fibres and nerve cell bodies in the ileum was also studied. CGRP-IR enteric neurons were morphometrically
analysed in myenteric (MP) and submucosal plexuses (SMP) of lambs (2–4 months). Sensory neurons retrogradely labelled with
FB were scattered in T5-L4 DRG but most were located at the upper lumbar levels (L1-L3); only a minor component of the extrinsic
afferent innervation of the ileum was derived from nodose ganglia. In the DRG, 57% of retrogradely labelled neurons were also
CGRP-IR. In cryostat sections, a dense network of CGRP-IR fibres was observed in the lamina propria beneath the epithelium,
around the lacteals and lymphatic follicles (Peyer's platches), and along and around enteric blood vessels. Rare CGRP-IR fibres
were also present in both muscle layers. Dense pericellular baskets of CGRP-IR fibres were observed around CGRP-negative somata.
The only CGRP-IR nerve cells were well-defined Dogiel type II neurons localised in the MP and in the external and internal
components of the SMP. CGRP-IR neurons in the myenteric ganglia were significantly larger than those in the submucosal ganglia
(mean profile areas: about 1,400 μm2 for myenteric neurons, 750 μm2 for submucosal neurons). About 6% of myenteric neurons and 25% of submucosal neurons were CGRP-IR Dogiel type II neurons.
The percentages of CGRP-IR neurons that were also tachykinin-IR were about 9% (MP) and 42% (SMP), whereas no CGRP-IR neurons
exhibited immunoreactivity for vasoactive intestinal peptide, nitric oxide synthase or tyrosine hydroxylase in either plexus.
Thus, CGRP immunoreactivity occurs in the enteric nervous system of the sheep ileum (as in human small intestine and MP of
pig ileum) in only one morphologically defined type of neuron, Dogiel type II cells. These are probably intrinsic primary
afferent neurons.
This work was supported by grants from the Ricerca Fondamentale Orientata (RFO) and Fondazione Del Monte di Bo e Ra. 相似文献
226.
Diana P Carbone A Barraja P Martorana A Gia O DallaVia L Cirrincione G 《Bioorganic & medicinal chemistry letters》2007,17(22):6134-6137
A series of 10 bis-indolylpyrazoles of type 9, 10 were obtained by cyclization of diketones 8 using hydrazine monohydrate or methylhydrazine in refluxing acetic acid/THF. Derivatives 9a,c,d were selected, by the National Cancer Institute (NCI, Bethesda, USA), to be evaluated against the full panel of about 60 human tumor cell lines derived from nine human cancer cell types and showed antiproliferative activity in the micromolar range. In particular, 9d, the most active compound was effective against all the tested cell lines with a GI(50) mean value of 3.23 microM; TGI and LC(50) values were 14.5 and 58.9 microM having positive response on 91% and 41% of the tested cell lines, respectively. 相似文献
227.
Piepoli A Schirru E Mastrorilli A Gentile A Cotugno R Quitadamo M Merla A Congia M Usai Satta P Perri F 《Journal of biomolecular screening》2007,12(5):733-739
Adult-type hypolactasia results from the progressive decline of lactase-phlorizin hydrolase activity in enterocytes after weaning. Lactase nonpersistence may determine a primary lactose intolerance with reduced diary product consumption, which is possibly related to an increased risk of colon cancer. Recently, a genetic variant C/T(-13910) upstream of the lactase-phlorizin hydrolase (LCT) gene has been strongly correlated with the lactase persistence/nonpersistence trait in both family and case-control studies. The authors validate a denaturing high-performance liquid chromatography (dHPLC)-based assay versus conventional genotype sequencing in detecting the C/T(-13910) polymorphism of LCT and evaluate its prevalence in 2 different Italian geographical areas and in colorectal cancer patients. DNA samples of 157 healthy subjects and 124 colon cancer patients from Apulia and of 97 healthy subjects from Sardinia were evaluated for the C/T(-13910) polymorphism by dHPLC, sequencing, and restriction fragment length polymorphism (RFLP). Under optimized conditions, dHPLC was as sensitive as DNA sequencing and detected a new genetic variant (T/C(-13913)) in 2 individuals that was not identified by RFLP assay. Frequency of lactase nonpersistence genotype (C/C(-13910)) was similar in healthy subjects from 2 different Italian geographical areas and not increased in patients with colorectal cancer. The results indicate that the dHPLC method may be used as a rapid, noninvasive, and labor-saving screening tool for genotyping C/T(-13910) polymorphism, with high success, low cost, and reproducibility. 相似文献
228.
Brescini Lucia Mazzanti Sara Morroni Gianluca Pallotta Francesco Masucci Annamaria Orsetti Elena Montalti Roberto Barchiesi Francesco 《Mycopathologia》2022,187(2-3):181-188
Mycopathologia - Candidemia is an alarming problem in critically ill patients including those admitted in Internal Medicine Wards (IMWs). Here, we analyzed all cases of candidemia in adult patients... 相似文献
229.
The production of enterocin 1146, a bacteriocin from Enterococcus faecium DPC1146, was studied during batch fermentation at pH 5, 5.5, 6 and 6.5. The bacteriocin was produced throughout the growth of the micro-organism, showing primary metabolite kinetics. Bacteriocin production stopped at the end of growth and was followed by a decrease in activity due primarily to adsorption on the cells of the producer. The optimal pH for enterocin 1146 production was 5.5, because of higher bacteriocin yield per unit of biomass and slower adsorption/degradation, while optimal pH for growth was between 6.0 and 6.5. 相似文献
230.
Lucia Anna Muscarella Raffaela Barbano Vincenzo D'Angelo Massimiliano Copetti Michelina Coco Teresa Balsamo Annamaria la Torre Angelo Notarangelo Michele Troiano Salvatore Parisi Nadia Icolaro Domenico Catapano Vanna Maria Valori Fabio Pellegrini Giuseppe Merla Massimo Carella Vito Michele Fazio Paola Parrella 《Epigenetics》2011,6(3):317-325