Identification of a circular RNA isoform of WASHC2A as a prognostic factor for high-risk paediatric B-ALL patients.

Pediatric B-cell acute lymphoblastic leukemia (B-ALL) is a serious disease for which a better understanding of prognostic factors and new therapeutic targets is needed. Circular RNAs (circRNAs) are promising markers due to their stability and differential expression patterns in various diseases. However, their role in pediatric B-ALL patients, particularly in risk stratification and relapse prediction, remains poorly understood.

LINC00958 as new diagnostic and prognostic biomarker of childhood acute lymphoblastic leukaemia of B cells.

Background: Paediatric acute B-cell lymphoblastic leukaemia is the most common cancer of the paediatric age. Although the advancement of scientific and technological knowledge has ensured a huge step forward in the management of this disease, there are 15%-20% cases of recurrence leading to serious complications for the patient and sometimes even death. It is therefore necessary to identify new and increasingly personalised biomarkers capable of predicting the degree of risk of B-ALL in order to allow the correct management of paediatric leukaemia patients.

Generation of an induced pluripotent stem cell line (CSS012-A (7672)) carrying the p.G376D heterozygous mutation in the TARDBP protein.

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative condition with phenotypic and genetic heterogeneity. It is characterized by the selective vulnerability and the progressive loss of the neural population. Here, an induced pluripotent stem cell (iPSC) line was generated from dermal fibroblasts of an individual carrying the p.

Generation of an induced pluripotent stem cell line, CSSi011-A (6534), from an Amyotrophic lateral sclerosis patient with heterozygous L145F mutation in SOD1 gene.

Among the known causative genes of familial ALS, SOD1mutation is one of the most common. It encodes for the ubiquitous detoxifying copper/zinc binding SOD1 enzyme, whose mutations selectively cause motor neuron death, although the mechanisms are not as yet clear. What is known is that mutant-mediated toxicity is not caused by loss of its detoxifying activity but by a gain-of-function.

GKN1 expression in gastric cancer cells is negatively regulated by miR-544a.

Gastrokine1 (GKN1), important for maintaining the physiological function of the gastric mucosa, is highly expressed in the stomach of healthy individuals but is down-regulated or absent in gastric tumor tissues and derived cell lines. The mechanisms underlying GKN1 gene inactivation are still unknown. We previously showed that GKN1 downregulation in gastric tumors is likely associated with an epigenetic transcriptional complex that negatively regulates GKN1 expression.

Generation of induced pluripotent stem cell line CSSi008-A (4698) from a patient affected by advanced stage of Dentato-Rubral-Pallidoluysian atrophy (DRPLA).

Dentato-Rubral-pallidoluysian atrophy (DRPLA) is a rare autosomal, dominant, progressive neurodegenerative disease that causes involuntary movements, mental and emotional problems. DRPLA is caused by a mutation in the ATN1 gene that encodes for an abnormal polyglutamine stretch in the atrophin-1 protein. DRPLA is most common in the Japanese population, where it has an estimated incidence of 2 to 7 per million people.

Production and characterization of human induced pluripotent stem cells (iPSC) CSSi007-A (4383) from Joubert Syndrome.

Joubert syndrome (JS) is an autosomal recessive neurodevelopmental disorder, characterized by congenital cerebellar and brainstem defects, belonging to the group of disorders known as ciliopathies, which are caused by mutations in genes encoding proteins of the primary cilium and basal body. Human induced pluripotent stem cells (hiPSCs) from a patient carrying a homozygous missense mutation (c.2168G > A) in AHI1, the first gene to be associated with JS, were produced using a virus-free protocol.

Establishment of stable iPS-derived human neural stem cell lines suitable for cell therapies.

Establishing specific cell lineages from human induced pluripotent stem cells (hiPSCs) is vital for cell therapy approaches in regenerative medicine, particularly for neurodegenerative disorders. While neural precursors have been induced from hiPSCs, the establishment of hiPSC-derived human neural stem cells (hiNSCs), with characteristics that match foetal hNSCs and abide by cGMP standards, thus allowing clinical applications, has not been described. We generated hiNSCs by a virus-free technique, whose properties recapitulate those of the clinical-grade hNSCs successfully used in an Amyotrophic Lateral Sclerosis (ALS) phase I clinical trial.

Copy number variations in healthy subjects. Case study: iPSC line CSSi005-A (3544) production from an individual with variation in 15q13.3 chromosome duplicating gene CHRNA7.

CHRNA7, encoding the neuronal alpha7 nicotinic acetylcholine receptor (a7nAChR), is highly expressed in the brain, particularly in the hippocampus. It is situated in the 15q13.3 chromosome region, frequently associated with a Copy Number Variation (CNV), which causes its duplication or deletion.

Production and characterization of CSSI003 (2961) human induced pluripotent stem cells (iPSCs) carrying a novel puntiform mutation in RAI1 gene, Causative of Smith-Magenis syndrome.

Smith-Magenis syndrome (SMS) is a complex genetic disorder characterized by developmental delay, behavioural problems and circadian rhythm dysregulation. About 90% of SMS cases are due to a 17p11.2 deletion containing retinoic acid induced1 (RAI1) gene, 10% are due to heterozygous mutations affecting RAI1 coding region.

Production and characterization of human induced pluripotent stem cells (iPSCs) from Joubert Syndrome: CSSi001-A (2850).

Joubert Syndrome (JS) is a rare autosomal recessive or X-linked condition characterized by a peculiar cerebellar malformation, known as the molar tooth sign (MTS), associated with other neurological phenotypes and multiorgan involvement. JS is a ciliopathy, a spectrum of disorders whose causative genes encode proteins involved in the primary cilium apparatus. In order to elucidate ciliopathy-associated molecular mechanisms, human induced pluripotent stem cells (hiPSCs) were derived from a patient affected by JS carrying a homozygous missense mutation in the AHI1 gene (p.

Role of human GKN1 on APP processing in gastric cancer.

Gastrokine 1 (GKN1) is highly expressed in gastric tissue and is secreted into the stomach but is not expressed in gastric cancer. GKN1 belongs to the BRICHOS domain family and plays a major role in maintaining gastric mucosa integrity. We previously demonstrated that a recombinant human GKN1 protein was able to interact with the amyloid precursor protein (APP) and was endowed with an anti-amyloidogenic property because it inhibited polymerization of the Aβ(1-40) peptide released from APP upon its partial hydrolysis.

Epigenetic alterations of gastrokine 1 gene expression in gastric cancer.

The gastrokine 1 (GKN1) protein is important for maintaining the physiological function of the gastric mucosa. GKN1 is down-regulated in gastric tumor tissues and derived cell lines and its over-expression in gastric cancer cells induces apoptosis, suggesting a possible role for the protein as a tumor suppressor. However, the mechanism by which GKN1 is inactivated in gastric cancer remains unknown.

Gastrokine 1 mRNA in human sera is not informative biomarker for gastric cancer.

Background: We aimed to ascertain if Gastrokine 1 mRNA in the sera of patients with gastric cancer might be an informative biomarker for the disease.

Results: Analysis of GKN1 mRNA in serum samples from healthy individuals (n = 23) and from patients with diagnosis of gastric cancer (n = 16), performed by using absolute quantification based on standard curve method, did not show any significative statistical difference between the two unpaired group of individuals.

Conclusions: Our preliminary results did not confirm GKN1 as a potential biomarker for gastric cancer.

AMP18 interacts with the anion exchanger SLC26A3 and enhances its expression in gastric cancer cells.

AMP18 is a stomach-specific secreted protein expressed in normal gastric mucosa but absent in gastric cancer. AMP18 plays a major role in maintaining gastric mucosa integrity and is characterized by the presence of a BRICHOS domain consisting of about 100 amino acids, present also in several unrelated proteins, and probably endowed with a chaperon-like activity. In this work, we exploited a functional proteomic strategy to identify potential AMP18 interactors with the aim to add knowledge on its functional role within gastric cell lines and tissues.

Ectopic expression of gastrokine 1 in gastric cancer cells up-regulates tight and adherens junction proteins network.

Gastrokine 1 (GKN1) is a stomach-specific protein important in the replenishment of the surface lumen epithelial cell layer and in maintaining mucosal integrity. A role in cell proliferation and differentiation has also been hypothesized. Despite these findings, the function(s) as well as the cellular localization of GKN1 in the cellular machinery are currently not clarified.

Anti-amyloidogenic property of human gastrokine 1.

Gastrokine 1 (GKN1) is a stomach-specific protein expressed in normal gastric tissue but absent in gastric cancer. GKN1 plays a major role in maintaining gastric mucosa integrity and is characterized by the presence of a BRICHOS domain consisting of about 100 amino acids also found in several unrelated proteins associated with major human diseases like BRI2, related to familial British and Danish dementia and surfactant protein C (SP-C), associated with respiratory distress syndrome. It was reported that recombinant BRICHOS domains from BRI2 and SP-C precursor (proSP-C) prevent fibrils formation of amyloid-beta peptide (Aβ), that is the major component of extracellular amyloid deposits in Alzheimer's disease.

Structural characterization and biological properties of human gastrokine 1.

Gastrokine-1 (GKN1), a protein expressed in normal gastric tissue, but absent in gastric cancer tissues and derived cell lines, has recently emerged as a potential biomarker for gastric cancer. To better establish the molecular properties of GKN1, the first protocol for the production of mature human GKN1 in the expression system of Pichia pastoris was settled. The recombinant protein showed anti-proliferative properties specifically on gastric cancer cell lines thus indicating that it was properly folded.