Characterization of farnesyl diphosphate farnesyl transferase 1 (FDFT1) expression in cancer.

To help characterize the FDFT1 gene and protein expression in cancer. Cholesterol represents an important structural component of lipid rafts. These specializations can be involved in pathways stimulating cell growth, survival and other processes active in cancer.

Update on the clinical utility of an RNA interference-based treatment: focus on Patisiran.

RNA interference (RNAi) is a naturally existing endogenous mechanism for post-transcriptional gene regulation, nowadays commonly utilized for functional characterization of genes and development of potential treatment strategies for diseases. RNAi-based studies for therapy, after being examined for over a decade, are finally in the pipeline for developing a potential treatment for the mutated transthyretin (TTR) gene, which gives rise to a dysfunctional TTR protein. This dysfunctional protein causes TTR amyloidosis (ATTR), an inherited, progressively incapacitating, and often fatal genetic disorder.

Target-based drug discovery for [Formula: see text]-globin disorders: drug target prediction using quantitative modeling with hybrid functional Petri nets.

Recent molecular studies provide important clues into treatment of [Formula: see text]-thalassemia, sickle-cell anaemia and other [Formula: see text]-globin disorders revealing that increased production of fetal hemoglobin, that is normally suppressed in adulthood, can ameliorate the severity of these diseases. In this paper, we present a novel approach for drug prediction for [Formula: see text]-globin disorders. Our approach is centered upon quantitative modeling of interactions in human fetal-to-adult hemoglobin switch network using hybrid functional Petri nets.

Validation of signalling pathways: Case study of the p16-mediated pathway.

p16 is recognized as a tumor suppressor gene due to the prevalence of its genetic inactivation in all types of human cancers. Additionally, p16 gene plays a critical role in controlling aging, regulating cellular senescence, detection and maintenance of DNA damage. The molecular mechanism behind these events involves p16-mediated signaling pathway (or p16- Rb pathway), the focus of our study.

NCI60 cancer cell line panel data and RNAi analysis help identify EAF2 as a modulator of simvastatin and lovastatin response in HCT-116 cells.

Simvastatin and lovastatin are statins traditionally used for lowering serum cholesterol levels. However, there exists evidence indicating their potential chemotherapeutic characteristics in cancer. In this study, we used bioinformatic analysis of publicly available data in order to systematically identify the genes involved in resistance to cytotoxic effects of these two drugs in the NCI60 cell line panel.

Genetic predisposition to β-thalassemia and sickle cell anemia in Turkey: a molecular diagnostic approach.

The thalassemia syndromes are a diverse group of inherited disorders that can be characterized according to their insufficient synthesis or absent production of one or more of the globin chains. They are classified in to α, β, γ, δβ, δ, and εγδβ thalassemias depending on the globin chain(s) affected. The β-thalassemias refer to that group of inherited hemoglobin disorders, which are characterized by a reduced synthesis (β(+)-thalassemia) or absence (β(0)-thalassemia) of beta globin (β-globin) chain production (1).

RNAi-based functional pharmacogenomics.

Experimental alteration of gene expression is a powerful technique for functional characterization of disease genes. RNA interference (RNAi) is a naturally occurring mechanism of gene regulation, which is triggered by the introduction of double-stranded RNA into a cell. This phenomenon can be synthetically exploited to down-regulate expression of specific genes by transfecting mammalian cells with synthetic short interfering RNAs (siRNAs).

Site-directed mutagenesis.

The technique of site-directed mutagenesis has been used to characterize gene and protein structure-function relationships, protein-protein interactions, binding domains of proteins, or active sites of enzymes for the last three decades. In this technique, a nucleotide sequence of interest is experimentally altered using synthetic oligonucleotides. The most commonly used approach is to use an oligonucleotide that is complementary to part of a single-stranded DNA template, but containing an internal mismatch to direct the mutation.

Differential subcellular expression of protein kinase C betaII in breast cancer: correlation with breast cancer subtypes.

Protein kinase C betaII (PKCβII) represents a novel potential target for anticancer therapies in breast cancer. In order to identify patient subgroups which might benefit from PKC-targeting therapies, we investigated the expression of PKCβII in human breast cancer cell lines and in a tissue microarray (TMA). We first screened breast cancer cell line representatives of breast cancer subtypes for PKCβII expression at the mRNA and at the protein levels.

Discovery of genetic profiles impacting response to chemotherapy: application to gemcitabine.

Chemotherapy is a major treatment modality for individuals affected by cancer. Currently, a number of genome-based technologies are being adopted to identify genes associated with drug response; however, large-scale genetic association applications are still limited. Here we describe a novel strategy based on the genetic and drug response data of the NCI60 cell lines to discover potential candidate genetic variants associated with variable response to chemotherapy.

Validation of short interfering RNA knockdowns by quantitative real-time PCR.

RNA interference (RNAi) is a natural mechanism, that is triggered by the introduction of double-stranded RNA into a cell. The long double-stranded RNA is then processed into short interfering RNA (siRNA) that mediates sequence-specific degradation of homologous transcripts. This phenomenon can be exploited to experimentally trigger RNAi and downregulate gene expression by transfecting mammalian cells with synthetic siRNA.

Intersex-like (IXL) is a cell survival regulator in pancreatic cancer with 19q13 amplification.

Pancreatic cancer is a highly aggressive disease characterized by poor prognosis and vast genetic instability. Recent microarray-based, genome-wide surveys have identified multiple recurrent copy number aberrations in pancreatic cancer; however, the target genes are, for the most part, unknown. Here, we characterized the 19q13 amplicon in pancreatic cancer to identify putative new drug targets.

Human SNPs resulting in premature stop codons and protein truncation.

Single nucleotide polymorphisms (SNPs) constitute the most common type of genetic variation in humans. SNPs introducing premature termination codons (PTCs), herein called X-SNPs, can alter the stability and function of transcripts and proteins and thus are considered to be biologically important. Initial studies suggested a strong selection against such variations/mutations.

Nonsense-mediated decay microarray analysis identifies mutations of EPHB2 in human prostate cancer.

The identification of tumor-suppressor genes in solid tumors by classical cancer genetics methods is difficult and slow. We combined nonsense-mediated RNA decay microarrays and array-based comparative genomic hybridization for the genome-wide identification of genes with biallelic inactivation involving nonsense mutations and loss of the wild-type allele. This approach enabled us to identify previously unknown mutations in the receptor tyrosine kinase gene EPHB2.