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Abstract : Function Shapes Content: DNA-Methylation Marker Genes and their Impact for Molecular Mechanisms of Glioma
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Abstract: Glioma is a clinically and biologically diverse disease. It challenges diagnosis and prognosis due to its molecular heterogeneity and diverse regimes of biological dysfunctions which are driven by genetic and epigenetic mechanisms. We discover the functional impact of sets of DNA methylation marker genes in the context of brain cancer subtypes as an exemplary approach how bioinformatics and particularly machine learning using self organizing maps (SOM) complements modern high-throughput genomic technologies. DNA methylation changes in gliomas comprise both, hyper- and hypomethylation in a subtype specific fashion. We compared pediatric (2 subtypes) and adult (4) glioblastoma and non-neoplastic brain. The functional impact of differential methylation marker sets is discovered in terms of gene set analysis which comprises a large collection of markers related to biological processes, literature data on gliomas and also chromatin states of the healthy brain. DNA methylation signature genes from alternative studies well agree with our signatures. SOM mapping of gene sets robustly identifies similarities between different marker sets even under conditions of noisy compositions. Mapping of previous sets of glioma markers reveals high redundancy and mixtures of subtypes in the reference cohorts. Consideration of the regulatory level of DNA methylation is inevitable for understanding cancer genesis and progression. It provides suited markers for diagnosis of glioma subtypes and disentangles tumor heterogeneity. Keywords: Glioma, molecular subtypes, DNA methylation, gene regulation, bioinformatics. Download Full Article |
Abstract : P53 Codon 72 and Endometrium Cancer
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Abstract: Background: The possible role p53 codon 72 in endometrium cancer has been investigated in several human populations: a positive association with the Pro variant has been observed in Asiatic but not in Caucasian populations. We reasoned that polymorphisms associated with endometrium cancer may interact with p53 codon 72 influencing the degree of association between this polymorphism and cancer. Methods: Sixty nine women admitted to the hospital for endometrium cancer and 473 healthy subjects were studied in the White population of Rome. Verbal consent was obtained from these subjects to participate to the study that was approved by the Department. P53 codon 72, ADA1, ADA6 and PTPN22 genotypes were determined by DNA analysis Statistical analysis were performed by using commercial software (SPSS). Results: The joint genotype carrying the *Pro allele of p53 codon 72and the ADA1*2 allele, the joint genotype carrying the *Pro allele and ADA6 *1 allele and the joint genotype carrying the *Pro allele and *C/*C genotype of PTPN22 show a proportion greater in cancer than in controls. The proportion of *Pro allele carriers in endometrium cancer shows a positive correlation (p=0.019) with the number of genetic factors considered i.e. ADA1,ADA6, PTPN22. Conclusion: Our data suggest that the strength of association between the disease and p53 codon 72 depends on other genetic factors. Thus the different patterns of association between p53 codon 72 and endometrium cancer observed among human populations could be at least in part related to differences in allelic frequencies of these genetic factors. Keywords: Endometrium cancer, p53 codon 72, ADA1, ADA6, PTPN22. Download Full Article |
Abstract : Nanodiagnostic and Nanotherapeutic Molecular Platforms for Cancer Management
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Abstract: Over the last ten years rapid progress is being made regarding the incorporation of nanoparticles in cancer diagnosis and treatment. Besides the limitations that have to be addressed, there are various research studies suggesting some promising nanodiagnostic and nanotherapeutic platforms for cancer managment. Nanotherapeutic platforms are based on the localized application of nanoparticles using targeting moieties, most usually antibodies, in order to in vivo direct nanoparticles to cancer cells. Thereafter, either nanoparticles react to external stimulus, for example under radiofrequency waves nanoparticles generate thermal energy, or they are used for targeted drug-delivery platforms, which allows the augmentation of drug concentration in the cancerous site of the body and thus minimizing side effects and increasing the efficacy of the drug. Regarding nanodiagnostics, particular focus is paid on nanoparticles that can act as contrast agents in cancer imaging for in vivo nanodiagnostics and on nanobiochips and nanobiosensor, devices that incorporate the “lab on a chip” notion for in vitro nanodiagnostics. In this review, several advanced nanodiagnostic and nanotherapeutic platforms are discussed, on the development of more effective and targeted molecular techniques in the diagnosis and treatment of cancer. Keywords: Nanotechnology, cancer, nanodiagnostics, nanotherapeutics. Download Full Article |
Abstract : Positive Association between the Polymorphic Variant CCND1 A870G and Colorectal Cancer in Ecuadorian Mestizo Population
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Abstract: Background: Colorectal cancer (CRC) is the fourth most common cause of cancer death worldwide and has an annual incidence of 917,000 cases. In Ecuador the CRC is the fifteenth most common form of cancer and the fourth leading cause of cancer deaths. Aim: Our goal was to establish frequencies related to the polymorphic variants: (CA)n in the EGFR gene and A870G in the CCND1 gene and their influence on the development of CRC in the Ecuadorian population. Methods: This is a retrospective case-control study consisting of colorectal cancer patients (n = 96 cancer tissues) compared to a control group (n = 62 adjacent healthy tissues). For the sequencing of the fragments, PCR and Sanger method was used. Results: The polymorphic variant A870G in CCND1 has a genotype frequency for the common homozygous G/G = 0.69, for the heterozygous A/G = 0.25 and for the less frequent homozygous A/A = 0.06 in the control group. We studied 7 alleles, repeats 14-19 have been reported in other studies, but the 13 repeats allele was first described here. The most common number of repetitions was 18 with a frequency of 0.326 in patients and 0.25 in controls (χ2 = 22.58, p <0.01). The odds ratio showed that the risk of developing colorectal cancer is 5 times greater if the individual is carrying the heterozygous G/A (p <0.01). Meanwhile, if the individual is carrying the allele 'A' the risk is 4 times more likely to develop this disease (p <0.01). Keywords: Colorectal cancer, CCND1, A870G, polymorphic association. Download Full Article |
