88 research outputs found
Analysis of extended genomic rearrangements in oncological research.
Screening for genomic rearrangements is a fundamental task in the genetic diagnosis of many inherited
disorders including cancer-predisposing syndromes. Several methods were developed for analysis of structural
genomic abnormalities, some are targeted to the analysis of one or few specific loci, others are designed to
scan the whole genome. Locus-specific methods are used when the candidate loci responsible for the specific
pathological condition are known. Whole-genome methods are used to discover loci bearing structural
abnormalities when the disease-associated locus is unknown. Three main approaches have been employed for
the analysis of locus-specific structural changes. The first two are based on probe hybridization and include
cytogenetics and DNA blotting. The third approach is based on PCR amplification and includes microsatellite or
single nucleotide polymorphism (SNP) genotyping, relative allele quantitation, real-time quantitative PCR, long
PCR and multiplex PCR-based methods such as multiplex ligation-dependent probe amplification and the
recently developed nonfluorescent multiplex PCR coupled to high-performance liquid chromatography analysis.
Whole-genome methods include cytogenetic methods, array-comparative genomic hybridization, SNP array
and other sequence-based methods. The goal of the present review is to provide an overview of the main
features and advantages and limitations of methods for the screening of structural genomic abnormalities
relevant to oncological research
Gastric adenomas: relationship between clinicopathological findings, Helicobacter pylori infection, APC mutations and COX-2 expression.
Gastric adenomas are rare neoplastic growths characterized by localized polypoid proliferations of dysplastic epithelium that tend to progress to infiltrating adenocarcinoma. Therefore, the identification of molecular markers that could reliably recognize adenomas at risk of progression is advocated in the clinical management. In this study we investigated, in a series of gastric adenoma specimens from an area at high risk of gastric cancer, the relationship between clinicopathological characteristics of adenoma and Helicobacter pylori infection, APC mutational status, and COX-2 and the down-stream enzyme mPGES1 expression. Helicobacter pylori infection, detected in 24%, and 33% by histology and PCR analyses, respectively, did not show any relationship with growth pattern, localization, size, dysplasia grade and presence of synchronous cancer. Pathogenetic mutations of MCR region (codons 1269-1589) of the APC gene were detected only in one case corresponding to a single, small size, low grade, H. pylori-negative adenoma. The expression of COX-2 largely matched that of mPGES(1). Both were overexpressed in 79% of cases showing a relationship with high-grade dysplasia, size >10 mm and presence of a synchronous carcinoma. In conclusion, COX-2 may play a key role in the development and progression of gastric adenoma and could be an attractive target in the management of gastric adenoma at major risk of cancer development
Domain-Wall Free-Energy of Spin Glass Models:Numerical Method and Boundary Conditions
An efficient Monte Carlo method is extended to evaluate directly domain-wall
free-energy for randomly frustrated spin systems. Using the method, critical
phenomena of spin-glass phase transition is investigated in 4d +/-J Ising model
under the replica boundary condition. Our values of the critical temperature
and exponent, obtained by finite-size scaling, are in good agreement with those
of the standard MC and the series expansion studies. In addition, two
exponents, the stiffness exponent and the fractal dimension of the domain wall,
which characterize the ordered phase, are obtained. The latter value is larger
than d-1, indicating that the domain wall is really rough in the 4d Ising spin
glass phase.Comment: 9 pages Latex(Revtex), 8 eps figure
Survival of hereditary non-polyposis colorectal cancer patients compared with sporadic colorectal cancer patients
<p>Abstract</p> <p>Background</p> <p>Patients with hereditary non-poliposys colorectal cancer (HNPCC) have better prognosis than sporadic colorectal cancer (CRC). Aim of our retrospective study was to compare the overall survival between sporadic CRC and HNPCC patients.</p> <p>Methods</p> <p>We analyzed a cohort of 40 (25 males and 15 females) HNPCC cases with a hospital consecutive series of 573 (312 males and 261 females) sporadic CRC observed during the period 1970–1993. In 15 HNPCC patients we performed mutational analysis for microsatellite instability. Survival rates were calculated by Kaplan-Meier method and compared with log rank test.</p> <p>Results</p> <p>The median age at diagnosis of the primary CRC was 46.8 years in the HNPCC series versus 61 years in sporadic CRC group. In HNPCC group 85% had a right cancer location, vs. 57% in the sporadic cancer group. In the sporadic cancer group 61.6% were early-stages cancer (Dukes' A and B) vs. 70% in the HNPCC group (p = ns). The crude 5-years cumulative survival after the primary CRC was 94.2% in HNPCC patients vs. 75.3% in sporadic cancer patients (p < 0.0001).</p> <p>Conclusion</p> <p>Our results show that overall survival of colorectal cancer in patients with HNPCC is better than sporadic CRC patients. The different outcome probably relates to the specific tumorigenesis involving DNA mismatch repair dysfunction.</p
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A low mortality, high morbidity Reduced Intensity Status Epilepticus (RISE) model of epilepsy and epileptogenesis in the rat
Animal models of acquired epilepsies aim to provide researchers with tools for use in understanding the processes underlying the acquisition, development and establishment of the disorder. Typically, following a systemic or local insult, vulnerable brain regions undergo a process leading to the development, over time, of spontaneous recurrent seizures. Many such models make use of a period of intense seizure activity or status epilepticus, and this may be associated with high mortality and/or global damage to large areas of the brain. These undesirable elements have driven improvements in the design of chronic epilepsy models, for example the lithium-pilocarpine epileptogenesis model. Here, we present an optimised model of chronic epilepsy that reduces mortality to 1% whilst retaining features of high epileptogenicity and development of spontaneous seizures. Using local field potential recordings from hippocampus in vitro as a probe, we show that the model does not result in significant loss of neuronal network function in area CA3 and, instead, subtle alterations in network dynamics appear during a process of epileptogenesis, which eventually leads to a chronic seizure state. The model’s features of very low mortality and high morbidity in the absence of global neuronal damage offer the chance to explore the processes underlying epileptogenesis in detail, in a population of animals not defined by their resistance to seizures, whilst acknowledging and being driven by the 3Rs (Replacement, Refinement and Reduction of animal use in scientific procedures) principles
Future research and collaboration: the “SINERGIE” project on HCV (South Italian Network for Rational Guidelines and International Epidemiology)
Modeling post-traumatic epilepsy for therapy development
Epilepsy is the most prevalent serious neurological disorder, afflicting almost 1% of the population worldwide. It is a heterogeneous disorder, comprising numerous syndromes with a wide range of etiologies, that is defined by the manifestation of chronic spontaneous recurrent seizures (CSRSs). An epileptic seizure, in turn, is defined by the International League Against Epilepsy (ILAE) as “transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain”. Post-traumatic epilepsy (PTE) arises after mechanical damage to the brain and is diagnosed when spontaneous seizures are observed at least a week after brain injury. PTE is the most prevalent acquired epilepsy in young adults and accounts for 5% of epilepsies overall. There are currently no cures for PTE and no means to prevent the disorder in those at risk. Available treatments of PTE are symptomatic, and at least 40% of patients have seizures that cannot be controlled with any of the available drugs. This dire situation requires rethinking the development and use
of animal models for the development of therapies for PTE. In this chapter we will introduce the problem and discuss several topics crucial for modeling PTE for therapy development
Resveratrol derivatives and their role as potassium channels modulators
A series of stilbenoid analogues of resveratrol (trans-3,4',5-trihydroxystilbene) with a stilbenic or a bibenzylic skeleton have been prepared by partial synthesis from resveratrol and dihydroresveratrol. The synthesized compounds have been evaluated for their ability to modulate voltage-gated channels
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