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At least 307 records · Page 17Linked to original sources
PubMed2004

Identification of tumor-associated plasma biomarkers using proteomic techniques: from mouse to human.

In an effort to identify tumor-associated proteins from plasma of tumor-bearing mice that may be used as diagnostic biomarkers, we developed a strategy that combines a tumor xenotransplantation model in nude mice with comparative proteomic technology. Five human cancer cell lines (SC-M1, HONE-1, CC-M1, OECM1, GBM 8401) derived from stomach, nasopharyngeal, colon, oral and brain cancers were subcutaneously inoculated into nude mice and compared to control nude mice injected with phosphate-buffered saline. One month later, plasma from mice inoculated with cancer cells was collected for proteomic analysis using two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS). Comparison of plasma 2-DE maps from tumor-bearing mice with those produced from control mice revealed the overexpression of several mouse acute phase proteins (APPs) such as haptoglobin. Another APP, serum amyloid A (SAA), was found only in mice bearing tumors induced by the stomach cancer cell line SC-M1, which has not previously been demonstrated in xenotransplatation experiment. Furthermore, by using immunohistochemistry, SAA and haptoglobin were found to originate from the mouse hosts and not from the human cancer cell line donors. The protein alterations were further confirmed on patients with stomach cancers where up-regulated levels of SAA were also observed. These results indicate that APPs may be used as nonspecific tumor-associated serum markers. SAA in particular may serve as a potential marker for detecting stomach cancer. Taken together, the combination of the xenotransplatation model in nude mice and proteomics analysis provided a valuable impact for clinical applications in cancer diagnostics. In addition, our findings demonstrate that a panel of APPs might serve as screening biomarkers for early cancer detection.

Amino Acid Sequence↗
PubMed2006

Proteomic analysis of tomato fruits from two ecotypes during ripening.

Ripening of climacteric fruits is a complex physiological phenomenon, which makes berries attractive/palatable and also determines their nutritional characteristics. We report here a comparative proteomic investigation on tomato fruits from a regional and commercial elite ecotype during maturation. Several hundreds of protein components were resolved on 2-DE gels (pH range 4-7) stained with colloidal Coomassie; almost 57% presented overlapping gel coordinates between the two compared varieties. Specific proteins were recognized in each ecotype as differentially expressed during ripening. Constant and variable components were excised, in-gel digested and analysed by MALDI-TOF-MS and microLC-ESI-IT-MS/MS approaches. Peptide MS and MS/MS data were searched against publicly available protein and EST databases, and 83 protein spots were unambiguously identified by MS. Gel matching procedures allowed further identification of proteins between ecotypes. In general, common variably expressed proteins in both ecotypes during maturation were associated to important physiological processes such as redox status control, defence, stress, carbon metabolism, energy production and cellular signalling. Protein components differentially expressed in each variety were also identified. The role of some of the identified proteins in the berries is discussed in relation to tomato fruit ripening. Accordingly, this investigation provides the first characterization of the tomato fruit proteome and description of its variation during maturation.

Gene Expression Profiling↗
PubMed2005

Down-regulation of S100C is associated with bladder cancer progression and poor survival.

PURPOSE: The goal of this study was to identify proteins down-regulated during bladder cancer progression. EXPERIMENTAL DESIGN: By using comparative proteome analysis and measurement of mRNA, we found a significant down-regulation of S100C, a member of the S100 family of proteins, in T24 (grade 3) as compared with RT4 (grade 1) bladder cancer cell lines. Moreover, quantification of the mRNA level revealed that decreased expression of the protein reflects a low level of transcription of the S100C gene. Based on this observation, we quantified the S100C mRNA expression level with real-time PCR in bladder cancer biopsy samples obtained from 88 patients followed for a median of 23 months (range, 1-97 months). RESULTS: We found a significantly lower mRNA expression of S100C in connective tissue invasive tumors (T1, P = 0.0030) and muscle invasive tumors [(T2-T4), P < 0.0001] compared with superficial tumors (Ta). A negative correlation between S100C and histopathologic grade (P = 0.0003) was also observed. Furthermore, the papillary type showed higher expression of S100C than did the solid type of the tumor (P < 0.0001). Importantly, we found that loss of S100C was associated with survival in bladder cancer patients (P = 0.0006). CONCLUSIONS: Our results show that low expression of S100C is associated with poor survival in patients with bladder cancer. Furthermore, loss of S100C in T1 as compared with Ta stage tumors emphasize that S100C expression is suppressed early during bladder cancer development.

Aged↗
PubMed2005

The effect of maternal asthma on placental and cord blood protein profiles.

OBJECTIVE: We conducted a comparative proteomic analysis of placental and umbilical cord blood proteins using surface-enhanced laser desorption ionization-time of flight mass spectrometry (SELDI-TOF MS) to examine the associations among asthma, fetal gender, and protein profiles. METHODS: Placental tissue and umbilical vein plasma were collected from 10 healthy and 20 asthmatic women. Placental proteins were extracted using phosphate-buffered saline containing protease inhibitors. Samples were applied to the surfaces of strong anion exchange (SAX2), weak cation exchange (WCX2) and immobilized metal affinity capture (IMAC-Cu(2+)) chips. Mass analysis was conducted using a Ciphergen Protein Biology System IIc (Freemont, CA), and differences in individual peak intensities between groups were determined. RESULTS: Fourteen placental peaks were significantly different between asthmatic and non-asthmatic women (seven more highly expressed and seven less highly expressed). Ten umbilical cord blood peak differences were identified, with four peaks more highly expressed and six peaks less highly expressed in asthmatics. Four placental and three umbilical cord blood proteins differed significantly between male and female fetuses. Two placental and five umbilical cord blood peaks were specifically increased in a subgroup of samples collected from asthmatic women who did not use inhaled glucocorticoids and were pregnant with a female fetus, a group previously found to have altered placental function. CONCLUSIONS: This study demonstrates the abilities of the SELDI technique as a tool for protein profiling in tissue or plasma. Further work to positively identify the candidate peptides found in this study may provide a greater understanding of the placental mechanisms leading to alterations in fetal growth in patients with bronchial asthma.

Adult↗
PubMed2006

Proteomic analysis of the cerebrospinal fluid of patients with lumbar disk herniation.

To better understand the pathophysiologic mechanisms underlying spinal nerve root injury induced by lumbar disk herniation (LDH), comparative proteomic analysis of cerebrospinal fluid (CSF) between patients with LDH (the experiment group) and the otherwise healthy patients who had had implants removed from healed fractures in the lower limbs (the control group) was carried out using 2-DE followed by LC-IT-MS and database searching. Image analysis of silver-stained 2-DE gels revealed that 15 protein spots showed significant differential expression between the two groups of CSF samples (p < 0.05). After searching the database we found that in CSF of LDH patients, the expression of cystatin C, apolipoprotein A-IV, vitamin D-binding protein, neurofilament triplet L protein, IgG, tetranectin, and hemoglobin were elevated. However, ProSAAS, prostagladin D2 synthase, creatine kinase B, superoxide dismutase 1 and peroxiredoxin 2 were decreased. The subsequent ELISA measured the concentration of tetranectin, vitamin D-binding protein and cystatin C and confirmed the results of proteomic analysis. These identified proteins are involved in the pathophysiological process of spinal nerve root injury caused by herniated lumbar disk. The functional implications of the alterations in the levels of these proteins are discussed in this paper.

Adult↗
PubMedDate not supplied

Proteome analysis in the study of lymphoma cells.

This review provides an overview on recent studies in the field of proteome analysis of lymphoma cells, and highlights the potentials of such studies for a better knowledge of drug effects at the molecular level. After giving general information on the field of proteome analysis of lymphoma cells, some characteristics of the strategies used during this analysis are pointed out, such as cell extraction strategies and affinity captures. Therefore, the issue of proteome analysis of lymphoma cells content will be covered with respect to those protein extracts that can be prepared in saline solutions, such as cytoplasm proteins, or that are associated with the cell membranes. The question of which kinds of information have been retrieved from lymphoma-cell proteomics is discussed on the basis of several examples-lymphoma cell-mapping studies and constitution of protein databases, and comparative proteome analysis studies of the modifications that result from a drug treatment.

Animals↗
PubMed2006

Heterologous expression and molecular and cellular characterization of CaPUB1 encoding a hot pepper U-Box E3 ubiquitin ligase homolog.

The U-box motif is a conserved domain found in the diverse isoforms of E3 ubiquitin ligase in eukaryotes. From water-stressed hot pepper (Capsicum annuum L. cv Pukang) plants, we isolated C. annuum putative U-box protein 1 (CaPUB1), which encodes a protein containing a single U-box motif in its N-terminal region. In vitro ubiquitination and site-directed mutagenesis assays revealed that CaPUB1 possessed E3 ubiquitin ligase activity and that the U-box motif was indeed essential for its enzyme activity. RNA gel-blot analysis showed that CaPUB1 mRNA was induced rapidly by a broad spectrum of abiotic stresses, including drought, high salinity, cold temperature, and mechanical wounding, but not in response to ethylene, abscisic acid, or a bacterial pathogen, suggesting its role in the early events in the abiotic-related defense response. Because transgenic work was extremely difficult in hot pepper, in this study we overexpressed CaPUB1 in Arabidopsis (Arabidopsis thaliana) to provide cellular information on the function of this gene in the development and plant responses to abiotic stresses. Transgenic Arabidopsis plants that constitutively expressed the CaPUB1 gene under the control of the cauliflower mosaic virus 35S promoter had markedly longer hypocotyls and roots and grew more rapidly than the wild type, leading to an early bolting phenotype. Microscopic analysis showed that 35S::CaPUB1 roots had increased numbers of small-sized cells, resulting in disordered, highly populated cell layers in the cortex, endodermis, and stele. In addition, CaPUB1-overexpressing plants displayed increased sensitivity to water stress and mild salinity. These results indicate that CaPUB1 is functional in Arabidopsis cells, thereby effectively altering cell and tissue growth and also the response to abiotic stresses. Comparative proteomic analysis showed that the level of RPN6 protein, a non-ATPase subunit of the 26S proteasome complex, was significantly reduced in 35SCaPUB1 seedlings as compared to the wild type. Pull-down and ubiquitination assays demonstrated that RPN6 interacted physically with CaPUB1 and was ubiquitinated in a CaPUB1-dependent manner in vitro. Although the physiological function of CaPUB1 is not yet clear, there are several possibilities for its involvement in a subset of physiological responses to counteract dehydration and high-salinity stresses in transgenic Arabidopsis seedlings.

Amino Acid Motifs↗
PubMed2003

Mapping the proteome of Leishmania Viannia parasites using two-dimensional polyacrylamide gel electrophoresis and associated technologies.

In this study we have demonstrated the potential of two-dimensional electrophoresis (2DE)-based technologies as tools for characterization of the Leishmania proteome (the expressed protein complement of the genome). Standardized neutral range (pH 5-7) proteome maps of Leishmania (Viannia) guyanensis and Leishmania (Viannia) panamensis promastigotes were reproducibly generated by 2DE of soluble parasite extracts, which were prepared using lysis buffer containing urea and nonidet P-40 detergent. The Coomassie blue and silver nitrate staining systems both yielded good resolution and representation of protein spots, enabling the detection of approximately 800 and 1,500 distinct proteins, respectively. Several reference protein spots common to the proteomes of all parasite species/strains studied were isolated and identified by peptide mass spectrometry (LC-ES-MS/MS), and bioinformatics approaches as members of the heat shock protein family, ribosomal protein S12, kinetoplast membrane protein 11 and a hypothetical Leishmania-specific 13 kDa protein of unknown function. Immunoblotting of Leishmania protein maps using a monoclonal antibody resulted in the specific detection of the 81.4 kDa and 77.5 kDa subunits of paraflagellar rod proteins 1 and 2, respectively. Moreover, differences in protein expression profiles between distinct parasite clones were reproducibly detected through comparative proteome analyses of paired maps using image analysis software. These data illustrate the resolving power of 2DE-based proteome analysis. The production and basic characterization of good quality Leishmania proteome maps provides an essential first step towards comparative protein expression studies aimed at identifying the molecular determinants of parasite drug resistance and virulence, as well as discovering new drug and vaccine targets.

Animals↗
PubMed2004

Proteomic approach: identification of Medicago truncatula proteins induced in roots after infection with the pathogenic oomycete Aphanomyces euteiches.

The legume root rot disease caused by the oomycete pathogen Aphanomyces euteiches is one major yield reducing factor in legume crop production. A comparative proteomic approach was carried out in order to identify proteins of the model legume Medicago truncatula which are regulated after an infection with A. euteiches . Several proteins were identified by two dimensional gel electrophoresis to be differentially expressed after pathogen challenge. Densitometric evaluation of expression values showed different regulation during the time-course analysed. Proteins regulated during the infection were identified by matrix assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS). Among the differentially expressed proteins, two encoded putative cell wall proteins and two were designated as small heat shock proteins. Furthermore, an isoform of the chalcone-O-methyltransferase was found to be increased in infected roots. The majority of induced proteins belonged to the family of class 10 of pathogenesis related proteins (PR10). Previously, various PR10-like proteins have been shown to be regulated by general stress or abscisic acid (ABA). Therefore, these proteins were further investigated concerning their regulation in response to drought stress and exogenous ABA-application. Complex regulation patterns were identified: three of the A. euteiches -induced PR10-like proteins were also induced by exogenous ABA- but none of them is induced after drought stress. In contrast, three of these proteins are down-regulated by drought stress. Hence, the strong expression of different PR10-family members and their regulation profiles indicates that this set of proteins plays a major role during root adaptations to various stress conditions.

Abscisic Acid↗
PubMed2003

Proteome analysis of the responses of Panax ginseng C. A. Meyer leaves to high light: use of electrospray ionization quadrupole-time of flight mass spectrometry and expressed sequence tag data.

We performed comparative proteomic analyses in order to understand the physiological responses of ginseng (Panax ginseng C. A. Meyer) to high light (HL). As a first step, we analyzed the proteins expressed in ginseng leaves. Proteins extracted from leaves were separated by two-dimensional polyacrylamide gel electrophoresis. Protein spots were identified by tandem mass spectra analysis using electrospray ionization quadrupole-time of flight mass spectrometry (ESI Q-TOF MS). We used a ginseng expressed sequence tag (EST) database as well as a nonredundant protein database from NCBI to identify proteins. Eighty-one proteins were identified using the nr protein database, 51 of which were also verified from the ginseng EST database. An additional 66 proteins were identified only from the ginseng EST database. Proteins that function in energy metabolism, protein stabilization, and protection against oxidative stress were abundant. To understand the light responses of ginseng leaves, we studied time dependent changes in expressed proteins produced by 0-4 h of HL exposure. Six HL-responsive proteins were identified: three proteins were up-regulated (cytosolic small heat-shock protein, cytosolic ascorbate peroxidase, and putative major latex-like protein) and three proteins were down-regulated (Rieske Fe/S protein, putative 3-beta hydroxysteroid dehydrogenase/isomerase-like protein, and oxygen-evolving enhancer-like protein). Our results show that the ginseng EST database combined with ESI Q-TOF MS analysis can be used to identify ginseng proteins and to elucidate the protective mechanism of ginseng against HL induced damage.

Amino Acid Sequence↗
PubMed2005

Proteomic analysis of somatic embryogenesis in Medicago truncatula. Explant cultures grown under 6-benzylaminopurine and 1-naphthaleneacetic acid treatments.

The Medicago truncatula line 2HA has a 500-fold greater capacity to regenerate plants in culture by somatic embryogenesis than wild-type Jemalong. We have compared proteomes of tissue cultures from leaf explants of these two lines. Both 2HA and Jemalong explants were grown on media containing the auxin 1-naphthaleneacetic acid and the cytokinin 6-benzylaminopurine. Proteins were extracted from the cultures at different time points (2, 5, and 8 weeks), separated by two-dimensional gel electrophoresis, and detected by silver staining. More than 2,000 proteins could be reproducibly resolved and detected on each gel. Statistical analysis showed that 54 protein spots were significantly (P < 0.05) changed in expression (accumulation) during the 8 weeks of culture, and most of these spots were extracted from colloidal Coomassie-stained two-dimensional gel electrophoresis gels and were subjected to matrix-assisted laser desorption ionization time-of-flight mass spectrometry or liquid chromatography-tandem mass spectrometry analysis. Using a publicly available expressed sequence tag database and the Mascot search engine, we were able to identify 16 differentially expressed proteins. More than 60% of the differentially expressed protein spots had very different patterns of gene expression between 2HA and Jemalong during the 8 weeks of culture.

Adenine↗
PubMed2004

Identification of proteins differentially expressed during chondrogenesis of mesenchymal cells.

We performed comparative proteome analysis of mesenchymal cells and chondrocytes to identify proteins differentially expressed during chondrogenesis. Nine such proteins were identified. Type II collagen, matrilin-1, carbonic anhydrase-II (CA-II), 3'-phosphoadenosine 5'-phosphosulfate (PAPS) synthetase-2, and aldo-keto reductase were increased during chondrogenesis, whereas cellular retinoic acid binding protein-I (CRABP-I), CRABP-II, cytoplasmic type 5 actin, and fatty acid binding protein were decreased or almost disappeared. Expression of type II collagen, matrilin-1, PAPS synthetase-2, and CA-II was regulated by extracellular signal-regulated protein kinase, protein kinase C, and p38 kinase, signaling molecules known to regulate chondrogenesis.

Animals↗
PubMed2005

Practical proteomic biomarker discovery: taking a step back to leap forward.

There is a pressing need for radically improved proteomic screening methods that allow for earlier diagnosis of disease, for systematic monitoring of physiological responses and for uncovering the fundamental mechanisms of drug action. Recent developments in proteomic technology offer tremendous, yet untapped, potential to yield novel biomarkers that are translatable to routine clinical use. Despite the significant conceptual promise of comparative proteomic profiling as a research platform for biomarker discovery, however, major hurdles remain for practical and clinical implementation. In particular, there is growing recognition that rigorous experimental design principles are urgently required to validate conclusively the unproven methodologies currently being touted. Debate and confusion persist about where the burden of proof lies: statistically, biologically or clinically? Moreover, there is no consensus about what constitutes a meaningful benchmark. An important question is how to achieve a scientifically rigorous, and therefore convincing, proof-of-concept that can be accepted by the field. Key analytical challenges related to these issues that must be addressed by the burgeoning biomarker community are discussed here.

Animals↗
PubMed2006

Proteome profiles of mucosal immunoglobulin uptake in inflamed porcine gut.

Acquisition of passive immunity by endocytosis of intact immunoglobulins (Ig) from colostrum is critical for prevention of intestinal and systemic diseases in neonatal mammals. We compared proteome patterns of healthy and inflamed gut tissues from pre-term piglets to investigate the effect of inflammation on acquisition of passive immunity. A clear difference in the two-dimensional gel electrophoresis protein patterns between healthy and inflamed intestinal tissues was observed, suggesting that inflamed tissues failed to absorb and transfer Ig from colostrum to epithelial cells. We have mapped and identified the Ig proteins that are taken up by healthy intestinal tissues, and found that isoforms of the IgA and IgG heavy chain and Ig kappa and lambda light chains were internalized. Our results indicate that colostrum protein uptake in the porcine gut is a selective process that is obstructed in inflamed pre-term gut.

Animals↗
PubMed2004

Expression proteomics identifies biochemical adaptations and defense responses in transgenic plants with perturbed polyamine metabolism.

Soluble proteins from leaves of transgenic tobacco plants with perturbed polyamine metabolism, caused by S-adenosylmethionine decarboxylase overexpression, were analysed by comparative proteomics. A group of proteins was found to be increasingly repressed, in parallel with the degree of polyamine perturbation, in each of the three independent transgenic lines. These were identified as isoforms of chloroplast ribonucleoproteins, known to be involved in chloroplast mRNA stability, processing and translation. Another group of eight proteins strongly induced in the most metabolically perturbed line was identified as multiple, uncharacterised isoforms of the defense protein PR-1, a known marker for systemic acquired resistance.

Acclimatization↗
PubMed2006

PHOG-BLAST--a new generation tool for fast similarity search of protein families.

BACKGROUND: The need to compare protein profiles frequently arises in various protein research areas: comparison of protein families, domain searches, resolution of orthology and paralogy. The existing fast algorithms can only compare a protein sequence with a protein sequence and a profile with a sequence. Algorithms to compare profiles use dynamic programming and complex scoring functions. RESULTS: We developed a new algorithm called PHOG-BLAST for fast similarity search of profiles. This algorithm uses profile discretization to convert a profile to a finite alphabet and utilizes hashing for fast search. To determine the optimal alphabet, we analyzed columns in reliable multiple alignments and obtained column clusters in the 20-dimensional profile space by applying a special clustering procedure. We show that the clustering procedure works best if its parameters are chosen so that 20 profile clusters are obtained which can be interpreted as ancestral amino acid residues. With these clusters, only less than 2% of columns in multiple alignments are out of clusters. We tested the performance of PHOG-BLAST vs. PSI-BLAST on three well-known databases of multiple alignments: COG, PFAM and BALIBASE. On the COG database both algorithms showed the same performance, on PFAM and BALIBASE PHOG-BLAST was much superior to PSI-BLAST. PHOG-BLAST required 10-20 times less computer memory and computation time than PSI-BLAST. CONCLUSION: Since PHOG-BLAST can compare multiple alignments of protein families, it can be used in different areas of comparative proteomics and protein evolution. For example, PHOG-BLAST helped to build the PHOG database of phylogenetic orthologous groups. An essential step in building this database was comparing protein complements of different species and orthologous groups of different taxons on a personal computer in reasonable time. When it is applied to detect weak similarity between protein families, PHOG-BLAST is less precise than rigorous profile-profile comparison method, though it runs much faster and can be used as a hit pre-selecting tool.

Algorithms↗
PubMed2006

Proteomic profiling and identification of immunodominant spore antigens of Bacillus anthracis, Bacillus cereus, and Bacillus thuringiensis.

Differentially expressed and immunogenic spore proteins of the Bacillus cereus group of bacteria, which includes Bacillus anthracis, Bacillus cereus, and Bacillus thuringiensis, were identified. Comparative proteomic profiling of their spore proteins distinguished the three species from each other as well as the virulent from the avirulent strains. A total of 458 proteins encoded by 232 open reading frames were identified by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry analysis for all the species. A number of highly expressed proteins, including elongation factor Tu (EF-Tu), elongation factor G, 60-kDa chaperonin, enolase, pyruvate dehydrogenase complex, and others exist as charge variants on two-dimensional gels. These charge variants have similar masses but different isoelectric points. The majority of identified proteins have cellular roles associated with energy production, carbohydrate transport and metabolism, amino acid transport and metabolism, posttranslational modifications, and translation. Novel vaccine candidate proteins were identified using B. anthracis polyclonal antisera from humans postinfected with cutaneous anthrax. Fifteen immunoreactive proteins were identified in B. anthracis spores, whereas 7, 14, and 7 immunoreactive proteins were identified for B. cereus and in the virulent and avirulent strains of B. thuringiensis spores, respectively. Some of the immunodominant antigens include charge variants of EF-Tu, glyceraldehyde-3-phosphate dehydrogenase, dihydrolipoamide acetyltransferase, Delta-1-pyrroline-5-carboxylate dehydrogenase, and a dihydrolipoamide dehydrogenase. Alanine racemase and neutral protease were uniquely immunogenic to B. anthracis. Comparative analysis of the spore immunome will be of significance for further nucleic acid- and immuno-based detection systems as well as next-generation vaccine development.

Antigens, Bacterial↗
PubMed2006

Proteomic analysis of nasal cells from cystic fibrosis patients and non-cystic fibrosis control individuals: search for novel biomarkers of cystic fibrosis lung disease.

Potential biological markers for cystic fibrosis (CF) lung disease were identified by comparative proteomics profiling of nasal cells from deletion of phenylalanine residue 508 (F508del)-homozygous CF patients and non-CF controls. From the non-CF 2-DE gels, 65 spots were identified by MS, and a reference 2-DE map was thus established. The majority of those correspond to ubiquitously expressed proteins. Consistent with the epithelial origin of this tissue, some of the identified proteins are epithelial markers (e.g. cytokeratins, palate lung and nasal epithelium clone protein (PLUNC), and squamous cell carcinoma antigen 1). Comparison of this protein profile with the one similarly obtained for CF nasal cells revealed a set of differentially expressed proteins. These included proteins related to chronic inflammation and some others involved in oxidative stress injury. Alterations were also observed in the levels of cytoskeleton proteins, being probably implicated with cytoskeleton organization changes described to occur in CF-airways. Lower levels were found for some mitochondrial proteins suggesting an altered mitochondrial metabolism in CF. Differential expression was also found for two more enzymes that have not been previously associated to CF. Further studies will clarify the involvement of such proteins in CF pathophysiology and whether they are targets for CF therapy.

Adolescent↗