Search results for "alternative"
showing 10 items of 1466 documents
BCL2 gene polymorphisms and splicing variants in chronic myeloid leukemia.
2015
Recent data suggest that constitutional genetic variation in the antiapoptotic BCL2 gene could be associated with the susceptibility to develop chronic myeloid leukemia (CML) and the clinical outcome in several hematological malignancies. The present study examines whether BCL2 single nucleotide polymorphisms (SNPs) predispose to CML or may potentially influence the disease characteristics at diagnosis. Notably, no association was observed between the four candidate BCL2 SNPs and the risk of developing CML. Instead, the 4777C>A (rs2279115) and the 5735A>G (rs1801018) SNPs were significantly associated with the disease risk profile as determined by the Sokal score. We found that such polymor…
The Muscleblind family of proteins: an emerging class of regulators of developmentally programmed alternative splicing.
2006
Alternative splicing is widely used to generate protein diversity and to control gene expression in many biological processes, including cell fate determination and apoptosis. In this review, we focus on the Muscleblind family of tissue-specific alternative splicing regulators. Muscleblind proteins bind pre-mRNA through an evolutionarily conserved tandem CCCH zinc finger domain. Human Muscleblind homologs MBNL1, MBNL2 and MBNL3 promote inclusion or exclusion of specific exons on different pre-mRNAs by antagonizing the activity of CUG-BP and ETR-3-like factors (CELF proteins) bound to distinct intronic sites. The relative activities of Muscleblind and CELF proteins control a key developmenta…
The Compass-like Locus, Exclusive to the Ambulacrarians, Encodes a Chromatin Insulator Binding Protein in the Sea Urchin Embryo
2013
Chromatin insulators are eukaryotic genome elements that upon binding of specific proteins display barrier and/or enhancer-blocking activity. Although several insulators have been described throughout various metazoans, much less is known about proteins that mediate their functions. This article deals with the identification and functional characterization in Paracentrotus lividus of COMPASS-like (CMPl), a novel echinoderm insulator binding protein. Phylogenetic analysis shows that the CMPl factor, encoded by the alternative spliced Cmp/Cmpl transcript, is the founder of a novel ambulacrarian-specific family of Homeodomain proteins containing the Compass domain. Specific association of CMPl…
A novel tumour associated leucine zipper protein targeting to sites of gene transcription and splicing
2002
We describe here the definition and characterization of antigen CT-8/HOM-TES-85 encoded by a previously unknown gene and identified by serological expression screening using antibodies from a seminoma patient. Intriguingly, the leucine zipper region of CT-8/HOM-TES-85 shows an atypical amphipathy with clusters of hydrophobic residues that is exclusively shared by the N-myc proto-oncogene. CT-8/HOM-TES-85 gene is tightly silenced in normal tissues except for testis. However, it is frequently activated in human neoplasms of different types including lung cancer, ovarian cancer, melanoma and glioma. Endogenous as well as heterogeneously expressed CT-8/HOM-TES-85 targets predominantly to the nu…
Exon-level expression analyses identify MYCN and NTRK1 as major determinants of alternative exon usage and robustly predict primary neuroblastoma out…
2012
BACKGROUND: Using mRNA expression-derived signatures as predictors of individual patient outcome has been a goal ever since the introduction of microarrays. Here, we addressed whether analyses of tumour mRNA at the exon level can improve on the predictive power and classification accuracy of gene-based expression profiles using neuroblastoma as a model. METHODS: In a patient cohort comprising 113 primary neuroblastoma specimens expression profiling using exon-level analyses was performed to define predictive signatures using various machine-learning techniques. Alternative transcript use was calculated from relative exon expression. Validation of alternative transcripts was achieved using q…
Development of resistance towards artesunate in MDA-MB-231 human breast cancer cells.
2011
Breast cancer is the most common cancer and the second leading cause of cancer death in industrialized countries. Systemic treatment of breast cancer is effective at the beginning of therapy. However, after a variable period of time, progression occurs due to therapy resistance. Artesunate, clinically used as anti-malarial agent, has recently revealed remarkable anti-tumor activity offering a role as novel candidate for cancer chemotherapy. We analyzed the anti-tumor effects of artesunate in metastasizing breast carcinoma in vitro and in vivo. Unlike as expected, artesunate induced resistance in highly metastatic human breast cancer cells MDA-MB-231. Likewise acquired resistance led to abol…
The FHIT gene is alternatively spliced in normal kidney and renal cell carcinoma.
1997
FHIT (Fragile Histidine Triad), a putative tumor suppressor gene, was cloned from fetal brain and colon cDNA libraries. Portions of this gene are deleted in esophageal, colon, lung and breast tumors, but this gene has not been found altered in sporadic renal cell carcinomas. We report here an alternatively spliced form of this gene cloned from a kidney cDNA library. This cDNA is 1189 bp in length, and contains an additional 94 bp exon, designated exon 2a (E2a). This novel sequence is located between exon 2 and exon 3 of the FHIT gene's untranslated region and exon 2a is present in all normal kidney tissues and cell lines. Analyses performed on sporadic renal cell carcinoma (RCC) tissues and…
Progression-free survival as an end-point in clinical trials of biotherapeutic agents
2007
Abstract Progression-free survival (PFS), the time from registration or randomisation of a patient until objective disease progression or death, can be considered as an outcome for clinical research and also as a basis for regulatory approval. Current experience suggests that greater standardisation and consistency are needed for clinical trials utilising PFS endpoints. To this end, the Biotherapy Development Association (BDA) convened a breakout session on the topic of PFS during its Third Alpine Meeting held 14–16 March 2007. Representatives of the pharmaceutical industry, regulatory agencies, academia, and patient advocacy groups identified challenges, developed recommendations, and work…
OFN Capital Budgeting Under Uncertainty and Risk
2017
The aim of this chapter is to propose a new approach to incorporating uncertainty into capital budgeting. The chapter presents methods that can be used by an investor when the decision maker wants to be able to make an investment decision where there are alternative investment projects. This kind of problem is undertaken under the conditions of uncertainty and risk using Ordered Fuzzy Numbers (OFN). The starting point is the concept of Ordered Fuzzy Numbers. The chapter illustrates the implementation of the proposed approach with an example where two alternative investment projects are analyzed. The authors present the capital budgeting problem using a numerical example. The described metho…
Expression of IAPs and alternative splice variants in hepatocellular carcinoma tissues and cells.
2005
IAPs (inhibitors of apoptosis proteins) might have a major role in the apoptotic resistance that marks many cancers. The studies on IAPs in human HCC have focused on survivin or XIAP, indicating that their new or increased expression in this tumor is associated with a more unfavorable prognosis. The present results corroborate these findings, emphasizing the role that the coordinated expression of different IAPs and alternative splice variants might play in the adverse biology of hepatocellular carcinoma.