Influence of ABCB1 and ABCG2 polymorphisms on the antiemetic efficacy in patients with cancer receiving cisplatin-based chemotherapy: a TRIPLE pharmacogenomics study.

Pharmacogenomics J. 2016 May 31;

Authors: Tsuji D, Yokoi M, Suzuki K, Daimon T, Nakao M, Ayuhara H, Kogure Y, Shibata K, Hayashi T, Hirai K, Inoue K, Hama T, Takeda K, Nishio M, Itoh K

Abstract
Resistance to antiemetic treatment with 5-hydroxytryptamine-3 receptor antagonist is an issue. This study evaluated the potential roles of ABCB1 and ABCG2 polymorphisms in antiemetic treatment resistance in patients with cancer previously enrolled in a randomized controlled trial. A total of 156 patients were evaluated for their responses to antiemetic therapy and then subdivided into granisetron or palonosetron groups. The genotypes were evaluated for their association with antiemetic efficacy in each treatment groups. Additional risk factors associated with complete response (CR) were examined using a multivariate regression analysis. No significant associations were identified for genetic polymorphisms in the palonosetron group. In the granisetron group, patients with ABCB1 2677TT and 3435TT genotypes had higher proportion of CR. In addition to ABCB1 polymorphisms, gender and cisplatin dose were associated with granisetron response by univariate analysis. Multivariate logistic regression analysis revealed that the ABCB1 3435C>T polymorphism and cisplatin dose were significant predictors of CR.The Pharmacogenomics Journal advance online publication, 31 May 2016; doi:10.1038/tpj.2016.38.

PMID: 27241063 [PubMed - as supplied by publisher]

Genetic variations in immunomodulatory pathways to predict survival in patients with locoregional gastric cancer.

Pharmacogenomics J. 2016 May 31;

Authors: Sunakawa Y, Cao S, Volz NB, Berger MD, Yang D, Parekh A, Zhang W, Matsusaka S, Ning Y, Stremitzer S, Stintzing S, Sebio A, Okazaki S, Wakatsuki T, Azuma M, Watanabe M, Koizumi W, Wu AH, Lenz HJ

Abstract
Immunomodulator-targeting therapies are under development in gastric cancer (GC). However, the role of genes modulating anti-tumor immunity in GC remains poorly understood. We investigated the association of variations in genes involved in immunomodulatory pathways with overall survival (OS) in locoregional GC patients. Extracted genomic DNA was analyzed for 35 functional single-nucleotide polymorphisms in genes, PDCD1, CD274, CTLA4, FOXP3, LAG3, ADORA2A, NT5E and IDO1, in 162 Japanese patients as discovery set and 277 US patients as validation set. The C allele of PDCD1 rs10204525 had univariate and multivariable associations with shorter OS in Japanese cohort (P=0.015, P=0.043, respectively). In US cohort the C allele predicted worse OS (P=0.007). Univariate and multivariable analyses revealed IDO1 rs9657182 associated with OS in the Japanese cohort; moreover, the association was confirmed in the US cohort. Genetic predisposition of the host in the immunomodulators may serve as a prognostic biomarker in patients with locoregional GC.The Pharmacogenomics Journal advance online publication, 31 May 2016; doi:10.1038/tpj.2016.46.

PMID: 27241062 [PubMed - as supplied by publisher]

Comparing cytochrome P450 pharmacogenetic information available on United States drug labels and European Union Summaries of Product Characteristics.

Pharmacogenomics J. 2016 May 31;

Authors: Reis-Pardal J, Rodrigues A, Rodrigues E, Fernandez-Llimos F

Abstract
Regulatory agencies are increasing the pharmacogenomic information in their official drug labeling. However, despite the importance of regulatory harmonization, this implementation may not be running in parallel among major agencies. Comparing labeling of medicines approved by different agencies may identify gaps to solve. Our study compared the cytochrome P450 pharmacogenetic information included in the United States (US) Food and Drug Administration (FDA) drug labels and European Union (EU) Summaries of Product Characteristics (SmPCs). US labels presented significantly more specific pharmacogenetic subheadings (51 vs 26%), more prevalence and pharmacokinetic data for each metabolic phenotype (59 vs 25% and 82 vs 48%, respectively) and more applicable information about dose modifications required (25 vs 5%). Approximately 75% of the US labels evaluated scored higher on the overall quality than the analogous EU SmPCs, and this difference was not associated with the time since the EU SmPCs' last review. To enhance harmonization, regulatory agencies should simultaneously introduce the pharmacogenetic information in their drug labeling.The Pharmacogenomics Journal advance online publication, 31 May 2016; doi:10.1038/tpj.2016.40.

PMID: 27241061 [PubMed - as supplied by publisher]

HLA-B18 as a risk factor of short-term progression to severe liver fibrosis in HIV/HCV co-infected patients with absent or minimal fibrosis: implications for timing of therapy.

Pharmacogenomics J. 2016 May 31;

Authors: Frías M, Rodríguez-Cano D, Cuenca-López F, Macías J, Gordon A, Manzanares-Martín B, Pineda JA, Camacho Á, Torre-Cisneros J, Peña J, Rivero-Juárez A, Rivero A

Abstract
Our aim was to analyze the influence of HLA-B haplotypes on liver fibrosis progression in HIV/hepatitis C virus (HCV) co-infected patients. Retrospective longitudinal study including HIV/HCV, non-cirrhotic and HCV treatment-naïve patients. The main outcome variable was liver fibrosis progression of at least one stage. One hundred and four patients constituted the study population (F0-F1: 62 (59.6%); F2: 22 (21.2%); F3: 20 (19.2%)). During a median follow-up of 54.5 months (IQR: 26.2-77), 45 patients (43.3%) showed an increase in the stage of liver fibrosis (time to event: 29 (IQR: 14-49.5) months). HLA-B18(pos) patients more frequently had a higher and faster fibrosis progression rate (73.3%; 24 (IQR: 8-29) months) than HLA-B18(neg) patients (38.2%; 34.5 (IQR: 14.7-51.2) months). This association was also observed in the development of F3-F4 fibrosis among F0-F2 patients (HLA-B18(pos): 69.2%; 18 (6.5-37) months vs HLA-B18(neg): 28.2%; 37 (IQR: 19-52) months). These results could impact the timing of HCV therapy in F0-F2 patients.The Pharmacogenomics Journal advance online publication, 31 May 2016; doi:10.1038/tpj.2016.42.

PMID: 27241060 [PubMed - as supplied by publisher]

Genetic epidemiology of pharmacogenetic variants in South East Asian Malays using whole-genome sequences.

Pharmacogenomics J. 2016 May 31;

Authors: Sivadas A, Salleh MZ, Teh LK, Scaria V

Abstract
Expanding the scope of pharmacogenomic research by including multiple global populations is integral to building robust evidence for its clinical translation. Deep whole-genome sequencing of diverse ethnic populations provides a unique opportunity to study rare and common pharmacogenomic markers that often vary in frequency across populations. In this study, we aim to build a diverse map of pharmacogenetic variants in South East Asian (SEA) Malay population using deep whole-genome sequences of 100 healthy SEA Malay individuals. We investigated the allelic diversity of potentially deleterious pharmacogenomic variants in SEA Malay population. Our analysis revealed 227 common and 466 rare potentially functional single nucleotide variants (SNVs) in 437 pharmacogenomic genes involved in drug metabolism, transport and target genes, including 74 novel variants. This study has created one of the most comprehensive maps of pharmacogenetic markers in any population from whole genomes and will hugely benefit pharmacogenomic investigations and drug dosage recommendations in SEA Malays.The Pharmacogenomics Journal advance online publication, 31 May 2016; doi:10.1038/tpj.2016.39.

PMID: 27241059 [PubMed - as supplied by publisher]

COMT val158met moderation of dopaminergic drug effects on cognitive function: a critical review.

Pharmacogenomics J. 2016 May 31;

Authors: Schacht JP

Abstract
The relationship between dopamine (DA) tone in the prefrontal cortex (PFC) and PFC-dependent cognitive functions (for example, working memory, selective attention, executive function) may be described by an inverted-U-shaped function, in which both excessively high and low DA is associated with impairment. In the PFC, the COMT val158met single nucleotide polymorphism (rs4680) confers differences in catechol-O-methyltransferase (COMT) efficacy and DA tone, and individuals homozygous for the val allele display significantly reduced cortical DA. Many studies have investigated whether val158met genotype moderates the effects of dopaminergic drugs on PFC-dependent cognitive functions. A review of 25 such studies suggests evidence for this pharmacogenetic effect is mixed for stimulants and COMT inhibitors, which have greater effects on D1 receptors, and strong for antipsychotics, which have greater effects on D2 receptors. Overall, COMT val158met genotype represents an enticing target for identifying individuals who are more likely to respond positively to dopaminergic drugs.The Pharmacogenomics Journal advance online publication, 31 May 2016; doi:10.1038/tpj.2016.43.

PMID: 27241058 [PubMed - as supplied by publisher]

Anti-tumor necrosis factor-α therapy in uveitis.

Surv Ophthalmol. 2015 Nov-Dec;60(6):575-89

Authors: Cordero-Coma M, Sobrin L

Abstract
Since the first reported use in 2001 of an anti-tumor necrosis factor-alpha (TNF-α) agent, infliximab, for the treatment of uveitis, several new anti-TNF-α agents have emerged for the treatment of refractory noninfectious uveitides, although their use remains off-label in the US. These agents have demonstrated remarkable clinical antiinflammatory efficacy and a potential immunoregulatory role in selected uveitis patients, but it is currently unclear whether they can modify the natural history of disease. We review the rationale and clinical indications for this therapy, the differences between agents, how to manage dosing and intervals, and how to screen for and identify potential side effects. We also present a summary of the science behind the use of anti-TNF-α agents in ocular inflammation and the evidence for their efficacy.

PMID: 26164735 [PubMed - indexed for MEDLINE]

Detection of Chromosomal Aberrations in Clinical Practice: From Karyotype to Genome Sequence.

Annu Rev Genomics Hum Genet. 2015;16:309-26

Authors: Martin CL, Warburton D

Abstract
Since the inception of clinical cytogenetics in the late 1950s, the field has witnessed the evolution of multiple methodologies for the evaluation of chromosomal imbalances and rearrangements. From the replacement of solidly stained chromosomes by Giemsa banding (G-banding) to in situ hybridization and microarrays, each technique has sought to detect smaller and smaller chromosomal aberrations across the genome. Microarray analysis has revealed that copy-number variants-a class of mutation resulting from the loss (deletion) or gain (duplication) of genomic material that is >1 kb in size-are among the significant contributors to human disease and normal variation. Here, we evaluate the history and utility of various methodologies and their impact on the current practice of clinical cytogenetics.

PMID: 26077817 [PubMed - indexed for MEDLINE]

Genome-wide microarray analysis of gene expression profiling in major depression and antidepressant therapy.

Prog Neuropsychopharmacol Biol Psychiatry. 2016 Jan 4;64:334-40

Authors: Lin E, Tsai SJ

Abstract
Major depressive disorder (MDD) is a serious health concern worldwide. Currently there are no predictive tests for the effectiveness of any particular antidepressant in an individual patient. Thus, doctors must prescribe antidepressants based on educated guesses. With the recent advent of scientific research, genome-wide gene expression microarray studies are widely utilized to analyze hundreds of thousands of biomarkers by high-throughput technologies. In addition to the candidate-gene approach, the genome-wide approach has recently been employed to investigate the determinants of MDD as well as antidepressant response to therapy. In this review, we mainly focused on gene expression studies with genome-wide approaches using RNA derived from peripheral blood cells. Furthermore, we reviewed their limitations and future directions with respect to the genome-wide gene expression profiling in MDD pathogenesis as well as in antidepressant therapy.

PMID: 25708651 [PubMed - indexed for MEDLINE]

MET network in PubMed: a text-mined network visualization and curation system.

Database (Oxford). 2016;2016

Authors: Dai HJ, Su CH, Lai PT, Huang MS, Jonnagaddala J, Rose Jue T, Rao S, Chou HJ, Milacic M, Singh O, Syed-Abdul S, Hsu WL

Abstract
Metastasis is the dissemination of a cancer/tumor from one organ to another, and it is the most dangerous stage during cancer progression, causing more than 90% of cancer deaths. Improving the understanding of the complicated cellular mechanisms underlying metastasis requires investigations of the signaling pathways. To this end, we developed a METastasis (MET) network visualization and curation tool to assist metastasis researchers retrieve network information of interest while browsing through the large volume of studies in PubMed. MET can recognize relations among genes, cancers, tissues and organs of metastasis mentioned in the literature through text-mining techniques, and then produce a visualization of all mined relations in a metastasis network. To facilitate the curation process, MET is developed as a browser extension that allows curators to review and edit concepts and relations related to metastasis directly in PubMed. PubMed users can also view the metastatic networks integrated from the large collection of research papers directly through MET. For the BioCreative 2015 interactive track (IAT), a curation task was proposed to curate metastatic networks among PubMed abstracts. Six curators participated in the proposed task and a post-IAT task, curating 963 unique metastatic relations from 174 PubMed abstracts using MET.Database URL: http://btm.tmu.edu.tw/metastasisway.

PMID: 27242035 [PubMed - in process]

Rapid Identification of Klebsiella pneumoniae by Matrix-Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry and Detection of Meropenem Resistance by Flow Cytometric Assay.

J Clin Lab Anal. 2016 May 30;

Authors: Kilic A, Dogan E, Kaya S, Oren S, Tok D, Ardic N, Baysallar M

Abstract
BACKGROUND: The aim of this study was to develop a rapid detection method of carbapenem-resistant Klebsiella pneumoniae (CRKP) strains both MALDI-TOF MS and flow cytometry (FCM).
METHODS: A total of 174 K. pneumoniae strains were included in this study. Molecular characterization of carbapenemase gene was performed by PCR. Bacterial identification was performed by MALDI-TOF-MS. Meropenem susceptibility was tested at the concentrations of breakpoints described by the Clinical and Laboratory Standards Institute (CLSI) guide by FCM.
RESULTS: Sixty-two CRKP were positive for at least one carbapenemase gene. A total of 174 K. pneumoniae isolates obtained from clinically relevant material were correctly identified by Bruker MALDI-TOF MS with log (score) >2.0. These results were 100% concordant with the Phoenix(™) Automated Microbiology System (BD, MD) and conventional identification results. Based on the analysis of the receiver operating characteristic (ROC) curves, the best validity and sensitivity data were obtained with a cut-off value of 18.88% by FCM. The concordance, sensitivity, and specificity for FCM by the selected cut-off values were 99.4%, 98.9%, and 100%, respectively.
CONCLUSIONS: We conclude that reliable results on bacterial identification and meropenem susceptibility test can be obtained within 2 hr combined by MALDI-TOF-MS and FCM.

PMID: 27239799 [PubMed - as supplied by publisher]

Appendicular mucinous adenocarcinoma associated with pseudomyxoma peritonei, a rare and difficult imaging diagnosis.

Med Ultrason. 2016 Jun;18(2):257-9

Authors: Chira RI, Nistor-Ciurba CC, Mociran A, Mircea PA

Abstract
Pseudomyxoma peritonei (PMP) is a rare disease, caused by primary mucinous tumors that arise most frequently from appendix, ovary, or pancreas. Usually diagnosis is made by computed tomography, but ultrasonography can be a very useful imagistic method, if this diagnosis is taken into account by the observer. We present a case of a PMP caused by an appendiceal mucinous carcinoma, in a 34-year-old male patient, with family history of malignancies, diagnosed in our department. He was thereafter surgically treated - appendiceal resection, peritoneal lavage - followed by chemotherapy. We underline the importance of ultrasonography, even though at first encounter, the diagnosis of PMP being generally difficult.

PMID: 27239665 [PubMed - in process]

Pigment Epithelium-Derived Factor (PEDF) is a Determinant of Stem Cell Fate: Lessons from an Ultra-Rare Disease.

J Dev Biol. 2015 Dec;3(4):112-128

Authors: Sagheer U, Gong J, Chung C

Abstract
PEDF is a secreted glycoprotein that is widely expressed by multiple organs. Numerous functional contributions have been attributed to PEDF with antiangiogenic, antitumor, anti-inflammatory, and neurotrophic properties among the most prominent. The discovery that null mutations in the PEDF gene results in Osteogenesis Imperfecta Type VI, a rare autosomal recessive bone disease characterized by multiple fractures, highlights a critical developmental function for this protein. This ultra-rare orphan disease has provided biological insights into previous studies that noted PEDF's effects on various stem cell populations. In addition to bone development, PEDF modulates resident stem cell populations in the brain, muscle, and eye. Functional effects on human embryonic stem cells have also been demonstrated. An overview of recent advances in our understanding by which PEDF regulates stem cells and their potential clinical applications will be evaluated in this review.

PMID: 27239449 [PubMed - as supplied by publisher]

Validation of the Korean Genome Epidemiology Study Risk Score to Predict Incident Hypertension in a Large Nationwide Korean Cohort.

Circ J. 2016 May 25;

Authors: Lim NK, Lee JW, Park HY

Abstract
BACKGROUND: This study aimed to validate the Korean Genome Epidemiology Study (KoGES) risk score to predict the 4-year risk of hypertension (HT) in a large nationwide sample, and compare its discrimination and calibration with the Framingham and blood pressure (BP)-only models.Methods and Results:This study analyzed 69,918 subjects without HT at baseline from the National Sample Cohort in the National Health Insurance Service database. We compared the Framingham, KoGES, and BP-only models for discrimination using area under the receiver-operating characteristic curves (AROC), calibration using goodness-of-fit tests, and reclassification ability using the continuous net reclassification improvement (NRI) and integrated discrimination improvement. Of 69,918 subjects, 18.6% developed HT during the follow-up. AROC was significantly higher for the KoGES (0.733) than for the Framingham (0.729) or BP-only (0.707) model. Recalibrated Framingham model underestimated HT incidence in all deciles (P<0.001). BP-only model overestimated risk in the lower deciles (P<0.001). KoGES model accurately predicted risk in all except the highest decile (χ(2)=14.85, P=0.062). The KoGES model led to a significant improvement in risk reclassification compared with the Framingham and BP-only models (NRI, 0.354; 95% confidence interval [CI], 0.343-0.365 and 0.542; 95% CI, 0.523-0.561, respectively).
CONCLUSIONS: In this validation study, the KoGES model demonstrated better discrimination, calibration, and reclassification ability than either the Framingham or BP-only model. The KoGES model may help identify Korean individuals at high risk for HT.

PMID: 27238835 [PubMed - as supplied by publisher]

Primary actinomycosis of breast-A diagnosis on cytology.

Diagn Cytopathol. 2016 May 30;

Authors: Gosavi AV, Anvikar AR, Sulhyan KR, Manek DD

Abstract
Primary actinomycosis of breast is a rare disease with only a few cases reported in the literature. We present a case of a 25-year-old lactating woman with primary actinomycosis of breast which was diagnosed on cytology. The patient presented with lump in left breast with dull aching pain. Fine-needle aspiration cytology smears showed acute suppurative inflammation with presence of fluffy basophilic colonies on Hematoxylin and Eosin staining and branched, Gram positive filamentous bacilli on Gram staining. The bacilli were non-acid fast with 1% Zeihl Neelsen stain. A diagnosis of actinomycosis was suggested on cytology. Histopathological examination revealed an abscess with few Gram positive basophilic granules surrounded by eosinophilic Splendore-Hoeppli material thus confirming the diagnosis of actinomycosis. Meticulous search for microorganisms with the aid of special stains should be done on cytology smears before labeling an inflammatory lesion as nonspecific. Diagn. Cytopathol. 2016. © 2016 Wiley Periodicals, Inc.

PMID: 27238823 [PubMed - as supplied by publisher]

Association of first-trimester angiogenic factors with placental histological findings in late-onset preeclampsia.

Placenta. 2016 Jun;42:44-50

Authors: Triunfo S, Crovetto F, Crispi F, Rodriguez-Sureda V, Dominguez C, Nadal A, Peguero A, Gratacos E, Figueras F

Abstract
OBJECTIVE: To explore in women with late-onset preeclampsia (PE) the association between maternal levels of angiogenic/antiangiogenic factors in the first trimester of pregnancy and histological findings attributable to placental underperfusion (PUP).
METHODS: A nested case-control cohort study was conducted in 73 women with pregnancies complicated by late-onset PE (>34 weeks at delivery) matched with controls. First trimester uterine artery Doppler (UtA); maternal levels of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were retrieved. Placentas were histologically evaluated using a hierarchical and standardized classification system. One-way ANOVA with linear polynomial contrast or linear-by-linear association test was performed to test the hypothesis of a linear association across study groups (controls, PE without PUP and PE with PUP).
RESULTS: In 54 (74%) placentas, 89 placental histological findings qualifying for PUP were found. Across study groups, significant values were observed in maternal levels of decreased PlGF (MoM values: 1.53, 1.41 and 1.37; p < 0.001), increased sFlt-1 (MoM values: 3.11, 3.11 and 3.22; p = 0.002), increased sFlt-1/PlGF ratio (MoM values: 2.3, 2.3 and 2.44; p < 0.001), abnormal UtA Doppler (MoM values: 1, 1.26 and 1.32; p < 0.001), and worse perinatal outcomes in terms of gestational age at delivery, cesarean section for not reassuring fetal status, birth weight and neonatal acidosis.
DISCUSSION: In late-onset PE an imbalance of circulating angiogenic and anti-angiogenic factors already present at 8-10 weeks of pregnancy was associated with histological findings reflecting placental insufficiency. An early first trimester screening by angiogenic factors might help to identify patients with placental involvement among late-onset PE cases.
CONCLUSION: In late-onset preeclampsia, first-trimester uterine Doppler and circulating levels of angiogenic/antiangiogenic factors are associated with placental underperfusion.

PMID: 27238713 [PubMed - in process]

A case of DIPNECH presenting as usual interstitial pneumonia.

Pneumonol Alergol Pol. 2016;84(3):174-7

Authors: Chatterjee K, Kamimoto JJ, Dunn A, Mittadodla E, Joshi M

Abstract
Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare disease that is classically described as presenting with cough, dyspnea, and wheezing in non-smoker middle aged females. Pulmonary function tests commonly demonstrate an obstructive pattern and CT of chest usually reveals diffuse air trapping with mosaic pattern. We present a case of patient with DIPNECH manifesting with restrictive pattern and as usual interstitial pneumonia on imaging.

PMID: 27238180 [PubMed - in process]

Discovery of a gamma heavy chain disease in a patient followed-up for a lymphoplasma cell proliferative disorder.

Ann Biol Clin (Paris). 2016 Jun 1;74(3):338-340

Authors: Humeau C, Monjanel H, Schellenberg F

Abstract
Gamma-heavy chains disease is a rare disease, with very few cases described in the literature. It is characterized by the presence of a monoclonal gamma-heavy chain without associated light chain. Its prevalence and prognosis are unknown. We report here the accidental discovery of a case of gamma-heavy chain disease during a pancytopenia exploration, performed in the hospital, in a patient known since 2002 for a lymphoplasmacytic type lymphoma first localized in bone marrow.

PMID: 27237805 [PubMed - as supplied by publisher]

The First Reported Case of Erdheim-Chester Disease in Egypt with Bilateral Exophthalmos, Loss of Vision, and Multi-Organ Involvement in a Young Woman.

Am J Case Rep. 2016;17:360-370

Authors: Abdellateef EE, Abdelhai AR, Gawish HH, Abdulmonaem GA, Abdelbary EH, Ahmed AI

Abstract
BACKGROUND Erdheim-Chester disease is a rare non-Langerhans-cell histiocytosis of unknown etiology with multi-organ involvement. CASE REPORT A 19-year-old woman presented with orthopnea, severe fatigue, bilateral exophthalmos, and gradual loss of vision. She had anemia and mild leucocytosis related to chronic illness. Marked left side pleural effusion and massive pericardial effusion with bilateral hydronephrosis were detected by plain X-ray, echocardiography, and computed tomography, respectively. Retro-orbital tissue and bone marrow biopsy revealed histiocytic infiltration, which was CD68-positive and CD1a-negative. CONCLUSIONS This report describes the first case presentation of Erdheim-Chester disease in our country. This case report may advance our understanding of an orphan disease. Our patient's young age and stable clinical status may allow long-term follow-up of treatment results.

PMID: 27237445 [PubMed - as supplied by publisher]

Comparative proteomics analysis of the antitumor effect of CIGB-552 peptide in HT-29 colon adenocarcinoma cells.

J Proteomics. 2015 Aug 3;126:163-71

Authors: Núñez de Villavicencio-Díaz T, Ramos Gómez Y, Oliva Argüelles B, Fernández Masso JR, Rodríguez-Ulloa A, Cruz García Y, Guirola-Cruz O, Perez-Riverol Y, Javier González L, Tiscornia I, Victoria S, Bollati-Fogolín M, Besada Pérez V, Guerra Vallespi M

Abstract
The second generation peptide CIGB-552 has a pro-apoptotic effect on H460 non-small cell lung cancer cells and displays a potent cytotoxic effect in HT-29 colon adenocarcinoma cells though its action mechanism is ill defined. Here, we present the first proteomic study of peptide effect in HT-29 cells using subcellular fractionation, protein and peptide fractionation by DF-PAGE and LC-MS/MS peptide identification. In particular, we explored the nuclear proteome of HT-29 cells at a 5h treatment identifying a total of 68 differentially modulated proteins, 49 of which localize to the nucleus. The differentially modulated proteins were analyzed following a system biology approach. Results pointed to a modulation of apoptosis, oxidative damage removal, NF-κB activation, inflammatory signaling and of cell adhesion and motility. Further Western blot and flow-cytometry experiments confirmed both pro-apoptotic and anti-inflammatory effects of CIGB-552 peptide in HT-29 cells.

PMID: 26013411 [PubMed - indexed for MEDLINE]