Biobank publications

Subscribe to Biobank publications feed Biobank publications
NCBI: db=pubmed; Term=biobank
Updated: 1 hour 31 min ago

Oncogenic activity of insulin in the development of non-small cell lung carcinoma.

Fri, 02/02/2018 - 12:55
Related Articles

Oncogenic activity of insulin in the development of non-small cell lung carcinoma.

Oncol Lett. 2018 Jan;15(1):447-452

Authors: Jiang J, Ren HY, Geng GJ, Mi YJ, Liu Y, Li N, Yang SY, Shen DY

Abstract
Insulin is associated with the progression of numerous different types of cancer. However, the association between insulin and non-small cell lung carcinoma (NSCLC) remains unknown. The aim of the present study was to evaluate the role of insulin in the proliferation, migration and drug resistance of NSCLC cells, and to determine whether the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway was involved. NSCLC cells were treated with insulin in the absence or presence of LY294002, an inhibitor of the PI3K/Akt pathway. Following co-incubation with insulin, cell proliferation and drug resistance were measured by MTT; cell migration was examined by wound healing and Transwell assays; and the expression of cyclin A, proliferating cell nuclear antigen (PCNA), p27, matrix metalloproteinase 3 (MMP3), P-gp and proteins involved in the PI3K/Akt pathway were assessed via western blotting. The results of the current study demonstrated that insulin enhanced the proliferation, migration and drug resistance of NSCLC cells. Correspondingly, insulin upregulated the expression of cyclin A, PCNA, MMP3, P-gp and downregulated p27 expression in NSCLC cells. Following treatment with insulin, it was demonstrated that phospho-Akt expression increased in a dose-dependent manner. However, the effects of insulin on NSCLC cells was inhibited by the PI3K/Akt pathway inhibitor LY294002. Therefore, the results of the current study indicate that insulin is associated with the development of NSCLC by activating the PI3K/Akt pathway. This may improve understanding of the mechanism of action of insulin in NSCLC in the future.

PMID: 29387228 [PubMed]

MET or NRAS amplification is an acquired resistance mechanism to the third-generation EGFR inhibitor naquotinib.

Fri, 02/02/2018 - 12:55
Related Articles

MET or NRAS amplification is an acquired resistance mechanism to the third-generation EGFR inhibitor naquotinib.

Sci Rep. 2018 Jan 31;8(1):1955

Authors: Ninomiya K, Ohashi K, Makimoto G, Tomida S, Higo H, Kayatani H, Ninomiya T, Kubo T, Ichihara E, Hotta K, Tabata M, Maeda Y, Kiura K

Abstract
As a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), osimeritnib is the standard treatment for patients with non-small cell lung cancer harboring the EGFR T790M mutation; however, acquired resistance inevitably develops. Therefore, a next-generation treatment strategy is warranted in the osimertinib era. We investigated the mechanism of resistance to a novel EGFR-TKI, naquotinib, with the goal of developing a novel treatment strategy. We established multiple naquotinib-resistant cell lines or osimertinib-resistant cells, two of which were derived from EGFR-TKI-naïve cells; the others were derived from gefitinib- or afatinib-resistant cells harboring EGFR T790M. We comprehensively analyzed the RNA kinome sequence, but no universal gene alterations were detected in naquotinib-resistant cells. Neuroblastoma RAS viral oncogene homolog (NRAS) amplification was detected in naquotinib-resistant cells derived from gefitinib-resistant cells. The combination therapy of MEK inhibitors and naquotinib exhibited a highly beneficial effect in resistant cells with NRAS amplification, but the combination of MEK inhibitors and osimertinib had limited effects on naquotinib-resistant cells. Moreover, the combination of MEK inhibitors and naquotinib inhibited the growth of osimertinib-resistant cells, while the combination of MEK inhibitors and osimertinib had little effect on osimertinib-resistant cells. Clinical assessment of this novel combination (MEK inhibitors and naquotinib) is worth considering in osimertinib-resistant lung tumors.

PMID: 29386539 [PubMed - in process]

Parental attitudes and expectations towards receiving genomic test results in healthy children.

Thu, 02/01/2018 - 14:50
Related Articles

Parental attitudes and expectations towards receiving genomic test results in healthy children.

Transl Behav Med. 2018 Jan 29;8(1):44-53

Authors: Kulchak Rahm A, Bailey L, Fultz K, Fan A, Williams JL, Buchanan A, Davis FD, Murray MF, Williams MS

Abstract
Little evidence is available to guide returning genomic results in children without medical indication for sequencing. Professional guidelines for returning information on adult-onset conditions are conflicting. The goal of this study was to provide preliminary information on parental attitudes and expectations about returning medically actionable genomic results in children who have been sequenced as part of a population biobank.Four focus groups of parents with a child enrolled in a population biobank were conducted. A deliberative engagement format included education about professional guidelines and ethical issues around returning results to children. Parents were presented two scenarios where their healthy child has a pathogenic variant for: (a) a medically actionable childhood condition; (b) a hereditary cancer syndrome with no medical management until adulthood. Thematic analysis was conducted on verbatim transcripts. Regardless of the scenario, parents stated that the genomic information was important, was like other unexpected medical information, and disclosure should be tailored to the child's age and result. Parents wanted the results in their child's medical record. Reasons for learning adult-onset results in their healthy children included to prepare their child for necessary medical action in adulthood. Parents also provided suggestions for program design. This preliminary evidence suggests that parents desire genomic results and expect to use this information to protect their child's health. More empirical research on psychosocial adjustment to such information with continued engagement of parents and children is needed to further inform how to best support families in the communication and use of genomic information.

PMID: 29385584 [PubMed - in process]

Soluble delta-like 1 homolog (DLK1) stimulates angiogenesis through Notch1/Akt/eNOS signaling in endothelial cells.

Thu, 02/01/2018 - 14:50
Related Articles

Soluble delta-like 1 homolog (DLK1) stimulates angiogenesis through Notch1/Akt/eNOS signaling in endothelial cells.

Angiogenesis. 2018 Jan 30;:

Authors: Huang CC, Kuo HM, Wu PC, Cheng SH, Chang TT, Chang YC, Kung ML, Wu DC, Chuang JH, Tai MH

Abstract
AIM: Delta-like 1 homolog (DLK1) is a non-canonical ligand of Notch signaling, which plays a pivotal role in vascular development and tumor angiogenesis. This study aimed to elucidate the function and mechanism of DLK1 in angiogenesis.
METHODS AND RESULTS: By using in situ hybridization and immunohistochemical studies, expression analysis revealed a unique vascular tropism of DLK1 in vasculature of neuroblastoma and vascular tumors. Thus, it was hypothesized that DLK1 may be cleaved and then bound to endothelial cells, thereby regulating the endothelial function. To test such hypothesis, soluble DLK1 encompassing DLK1 extracellular domain (DLK1-EC) was generated and validated by its inhibitory function in adipogenesis assay. Recombinant DLK1-EC exhibited the preferential binding capability toward endothelial cells and stimulated the microvessels sprouting in aorta rings. Above all, implantation of DLK1-EC dose-dependently elicited the cornea neovascularization in rats. By using various angiogenesis assays, it was delineated that DLK1-EC stimulated the angiogenesis by promoting the proliferation, motility and tube formation of endothelial cells. By immunoblot and luciferase analysis, it was elucidated that DLK1-EC enhanced the expression and activities of Notch1/Akt/eNOS/Hes-1 signaling in dose- and time-dependent manners. Pharmaceutical blockage of Notch signaling using γ-secretase inhibitor DAPT abrogated the DLK1-EC-induced endothelial migration and Hes-1-driven luciferase activities. Furthermore, Notch1 inactivation by neutralizing antibodies or RNA interference reversed the DLK1-EC-induced angiogenesis.
CONCLUSIONS: The present study unveils the pro-angiogenic function and mechanism of soluble DLK1 through activation of Notch1 signaling in endothelial cells.

PMID: 29383634 [PubMed - as supplied by publisher]

Association of Circulating Vitamin E (α- and γ-Tocopherol) Levels with Gallstone Disease.

Thu, 02/01/2018 - 14:50
Related Articles

Association of Circulating Vitamin E (α- and γ-Tocopherol) Levels with Gallstone Disease.

Nutrients. 2018 Jan 27;10(2):

Authors: Waniek S, di Giuseppe R, Esatbeyoglu T, Ratjen I, Enderle J, Jacobs G, Nöthlings U, Koch M, Schlesinger S, Rimbach G, Lieb W

Abstract
In addition to well-established risk factors like older age, female gender, and adiposity, oxidative stress may play a role in the pathophysiology of gallstone disease. Since vitamin E exerts important anti-oxidative functions, we hypothesized that circulating vitamin E levels might be inversely associated with prevalence of gallstone disease. In a cross-sectional study, we measured plasma levels of α- and γ-tocopherol using high performance liquid chromatography in a community-based sample (582 individuals; median age 62 years; 38.5% women). Gallstone disease status was assessed by ultrasound. Multivariable-adjusted logistic regression models were used to estimate the association of circulating α- and γ-tocopherol/cholesterol ratio levels with prevalent gallstone disease. Lower probabilities of having gallstone disease were observed in the top (compared to the bottom) tertile of the plasma α-tocopherol/cholesterol ratio in multivariable-adjusted models (OR (Odds Ratio): 0.31; 95% CI (Confidence Interval): 0.13-0.76). A lower probability of having gallstone disease was also observed for the γ-tocopherol/cholesterol ratio, though the association did not reach statistical significance (OR: 0.77; 95% CI: 0.35-1.69 for 3rd vs 1st tertile). In conclusion, our observations are consistent with the concept that higher vitamin E levels might protect from gallstone disease, a premise that needs to be further addressed in longitudinal studies.

PMID: 29382041 [PubMed - in process]

Association between body height and month of birth among women of European origin in northern and southern hemispheres.

Thu, 02/01/2018 - 14:50
Related Articles

Association between body height and month of birth among women of European origin in northern and southern hemispheres.

Am J Hum Biol. 2017 May 06;29(3):

Authors: Rosset I, Żądzińska E, Strapagiel D, Grzelak A, Henneberg M

Abstract
OBJECTIVES: The purpose of this study was to examine the potential association between month of birth and body height among women in northern and southern hemispheres.
METHODS: Body heights of adult women of European origin born between 1935 and 1981 who lived in Poland (N = 3,933) and in Australia (N = 1,118) were examined in relation to month of birth by analysis of variance.
RESULTS: No association between month of birth and body height was observed in either Polish or Australian women. For Polish women, a clear, statistically significant secular trend in body height was confirmed for the analyzed period (P < .0001). No such trend occurred among the Australian women.
CONCLUSIONS: Results do not confirm a significant association between month of birth and adult body height in women. It is, however, important to see a difference in secular trends, which was large in Polish women and nonexistent in Australian females.

PMID: 28094888 [PubMed - indexed for MEDLINE]

External validation of risk prediction models for incident colorectal cancer using UK Biobank.

Wed, 01/31/2018 - 12:12

External validation of risk prediction models for incident colorectal cancer using UK Biobank.

Br J Cancer. 2018 Jan 30;:

Authors: Usher-Smith JA, Harshfield A, Saunders CL, Sharp SJ, Emery J, Walter FM, Muir K, Griffin SJ

Abstract
BACKGROUND: This study aimed to compare and externally validate risk scores developed to predict incident colorectal cancer (CRC) that include variables routinely available or easily obtainable via self-completed questionnaire.
METHODS: External validation of fourteen risk models from a previous systematic review in 373 112 men and women within the UK Biobank cohort with 5-year follow-up, no prior history of CRC and data for incidence of CRC through linkage to national cancer registries.
RESULTS: There were 1719 (0.46%) cases of incident CRC. The performance of the risk models varied substantially. In men, the QCancer10 model and models by Tao, Driver and Ma all had an area under the receiver operating characteristic curve (AUC) between 0.67 and 0.70. Discrimination was lower in women: the QCancer10, Wells, Tao, Guesmi and Ma models were the best performing with AUCs between 0.63 and 0.66. Assessment of calibration was possible for six models in men and women. All would require country-specific recalibration if estimates of absolute risks were to be given to individuals.
CONCLUSIONS: Several risk models based on easily obtainable data have relatively good discrimination in a UK population. Modelling studies are now required to estimate the potential health benefits and cost-effectiveness of implementing stratified risk-based CRC screening.British Journal of Cancer advance online publication, 30 January 2018; doi:10.1038/bjc.2017.463 www.bjcancer.com.

PMID: 29381683 [PubMed - as supplied by publisher]

The interaction of genetic predisposition and socioeconomic position with type 2 diabetes mellitus: cross-sectional and longitudinal analyses from the Lifelines Cohort and Biobank Study.

Wed, 01/31/2018 - 12:12

The interaction of genetic predisposition and socioeconomic position with type 2 diabetes mellitus: cross-sectional and longitudinal analyses from the Lifelines Cohort and Biobank Study.

Psychosom Med. 2018 Jan 29;:

Authors: van Zon SKR, Reijneveld SA, van der Most PJ, Swertz MA, Bültmann U, Snieder H

Abstract
OBJECTIVE: A strong genetic predisposition for type 2 diabetes mellitus (T2DM) may aggravate the negative effects of low socioeconomic position (SEP) in the etiology of the disorder. This study aimed to examine cross-sectional and longitudinal associations and interactions of a genetic risk score (GRS) and SEP with T2DM, and to investigate whether clinical and behavioral risk factors can explain these associations and interactions.
METHODS: We used data from 13,027 genotyped participants from the Lifelines study. The GRS was based on single-nucleotide polymorphisms (SNPs) genome-wide associated with T2DM and was categorized into tertiles. SEP was measured as educational level. T2DM was based on biological markers, recorded medication use, and self-reports. Cross-sectional and longitudinal associations, and interactions, between the GRS and SEP on T2DM were examined.
RESULTS: The combination of a high GRS and low SEP had the strongest association with T2DM in cross-sectional (OR: 3.84; 95% CI: 2.28, 6.46) and longitudinal analyses (HR: 2.71; 1.39, 5.27), compared to a low GRS and high SEP. Interaction between a high GRS and a low SEP was observed in cross-sectional (relative excess risk due to interaction: 1.85; 0.65, 3.05) but not in longitudinal analyses. Clinical and behavioral risk factors mostly explained the observed associations and interactions.
CONCLUSIONS: A high GRS combined with a low SEP provides the highest risk for T2DM. These factors also exacerbated each other's impact cross-sectionally but not longitudinally. Preventive measures should target individual and contextual factors of this high-risk group to reduce the risk of T2DM.

PMID: 29381659 [PubMed - as supplied by publisher]

Associations between primary tumor RAS, BRAF and PIK3CA mutation status and metastatic site in patients with chemo-resistant metastatic colorectal cancer.

Wed, 01/31/2018 - 12:12

Associations between primary tumor RAS, BRAF and PIK3CA mutation status and metastatic site in patients with chemo-resistant metastatic colorectal cancer.

Acta Oncol. 2018 Jan 30;:1-6

Authors: Christensen TD, Palshof JA, Larsen FO, Poulsen TS, Høgdall E, Pfeiffer P, Jensen BV, Yilmaz MK, Nielsen D

Abstract
BACKGROUND: Several studies have investigated correlations between metastatic pattern and mutation status in patients with colorectal cancer (CRC). However, most of the studies were small and heterogeneously designed and further research is needed to confirm previous results. In this study, we investigated the association between RAS (KRAS or NRAS), BRAF, PIK3CA mutations and metastatic pattern in patients with metastatic (m) CRC.
MATERIAL AND METHODS: This study reviewed Danish biobank and database of patients with mCRC who received cetuximab and irinotecan, independent of RAS mutation status, after fluoropyrimidine, oxaliplatin and irinotecan treatment failure. The database contained information regarding tumor mutation status of KRAS, NRAS, BRAF and PIK3CA genes.
RESULTS: Totally, 448 patients were included. On multivariate analyses, RAS mutations were significantly associated with increased odds of having lung metastases at diagnosis of mCRC (odds ratio (OR) = 2.04; 95% confidence interval (CI) = 1.32-3.17), and PIK3CA mutations with decreased odds of peritoneal metastases at diagnosis of mCRC (OR = 0.10; 95%CI = 0.01-0.79). On multivariate analyses of the hazard of developing metastases at any time during follow-up, RAS mutations were significantly associated with increased hazard of lung (hazard ratio (HR) = 1.34; 95%CI = 1.04-1.72) and ovarian metastases (HR = 3.12; 95%CI = 1.05-9.24), BRAF V600E mutation was associated with increased hazard of skin metastases (HR = 6.82; 95%CI = 1.86-25.02) and PIK3CA mutations with decreased hazard of peritoneal metastases (HR = 0.31; 95%CI = 0.11-0.86).
CONCLUSIONS: This study indicated that in patients with mCRC, RAS mutations are associated with increased risk of lung and ovary metastases. BRAF V600E is associated with increased risk of skin metastases, and PIK3CA mutation with decreased risk of peritoneal metastases.

PMID: 29380640 [PubMed - as supplied by publisher]

Thyroid Hormone Promotes β-Catenin Activation and Cell Proliferation in Colorectal Cancer.

Wed, 01/31/2018 - 12:12

Thyroid Hormone Promotes β-Catenin Activation and Cell Proliferation in Colorectal Cancer.

Horm Cancer. 2018 Jan 29;:

Authors: Lee YS, Chin YT, Shih YJ, Nana AW, Chen YR, Wu HC, Yang YSH, Lin HY, Davis PJ

Abstract
Thyroid hormone status has long been implicated in cancer development. Here we investigated the role of thyroxine (T4) in colorectal cancer cell lines HCT 116 (APC wild type) and HT-29 (APC mutant), as well as the primary cultures of cancer cells derived from patients. Cell proliferation was evaluated with standard assay and proliferation marker expression. β-Catenin activation was examined according to nuclear β-catenin accumulation and β-catenin target gene expression. The results showed that T4 increased colorectal cancer cell proliferation while cell number and viability were elevated by T4 in both established cell lines and primary cells. Moreover, the transcriptions of proliferative genes PCNA, CCND1, and c-Myc were enhanced by T4 in the primary cells. T4 induced nuclear β-catenin accumulation, as well as high cyclin D1 and c-Myc levels compared to the untreated cells. In addition, the β-catenin-directed transactivation of CCND1 and c-Myc promoters was also upregulated by T4. CTNNB1 transcription was raised by T4 in HCT 116, but not in HT-29, while the boosted β-catenin levels were observed in both. Lastly, the T4-mediated gene expression could be averted by the knockdown of β-catenin. These results suggested that T4 promotes β-catenin activation and cell proliferation in colorectal cancer, indicating that an applicable therapeutic strategy should be considered.

PMID: 29380230 [PubMed - as supplied by publisher]

Glutaminyl cyclase activity correlates with levels of Aβ peptides and mediators of angiogenesis in cerebrospinal fluid of Alzheimer's disease patients.

Wed, 01/31/2018 - 12:12
Related Articles

Glutaminyl cyclase activity correlates with levels of Aβ peptides and mediators of angiogenesis in cerebrospinal fluid of Alzheimer's disease patients.

Alzheimers Res Ther. 2017 Jun 06;9(1):38

Authors: Bridel C, Hoffmann T, Meyer A, Durieux S, Koel-Simmelink MA, Orth M, Scheltens P, Lues I, Teunissen CE

Abstract
BACKGROUND: Pyroglutamylation of truncated Aβ peptides, which is catalysed by enzyme glutaminyl cyclase (QC), generates pE-Aβ species with enhanced aggregation propensities and resistance to most amino-peptidases and endo-peptidases. pE-Aβ species have been identified as major constituents of Aβ plaques and reduction of pE-Aβ species is associated with improvement of cognitive tasks in animal models of Alzheimer's disease (AD). Pharmacological inhibition of QC has thus emerged as a promising therapeutic approach for AD. Here, we question whether cerebrospinal fluid (CSF) QC enzymatic activity differs between AD patients and controls and whether inflammatory or angiogenesis mediators, some of which are potential QC substrates, and/or Aβ peptides may serve as pharmacodynamic read-outs for QC inhibition.
METHODS: QC activity, Aβ peptides and inflammatory or angiogenesis mediators were measured in CSF of a clinically well-characterized cohort of 20 mild AD patients, 20 moderate AD patients and 20 subjective memory complaints (SMC) controls. Correlation of these parameters with core diagnostic CSF AD biomarkers (Aβ42, tau and p-tau) and clinical features was evaluated.
RESULTS: QC activity shows a tendency to decrease with AD progression (p = 0.129). The addition of QC activity to biomarkers tau and p-tau significantly increases diagnostic power (ROC-AUCTAU = 0.878, ROC-AUCTAU&QC = 0.939 and ROC-AUCpTAU = 0.820, ROC-AUCpTAU&QC = 0.948). In AD and controls, QC activity correlates with Aβ38 (r = 0.83, p < 0.0001) and Aβ40 (r = 0.84, p < 0.0001), angiogenesis mediators (Flt1, Tie2, VEGFD, VCAM-1 and ICAM-1, r > 0.5, p < 0.0001) and core diagnostic biomarkers (r > 0.35, p = <0.0057). QC activity does not correlate with MMSE or ApoE genotype.
CONCLUSIONS: Aβ38, Aβ40 and angiogenesis mediators (Flt1, Tie2, VEGFD, VCAM-1 and ICAM-1) are potential pharmacodynamic markers of QC inhibition, because their levels closely correlate with QC activity in AD patients. The addition of QC activity to core diagnostic CSF biomarkers may be of specific interest in clinical cases with discordant imaging and biochemical biomarker results.

PMID: 28587659 [PubMed - indexed for MEDLINE]

Reduced miR-550a-3p leads to breast cancer initiation, growth, and metastasis by increasing levels of ERK1 and 2.

Wed, 01/31/2018 - 12:12
Related Articles

Reduced miR-550a-3p leads to breast cancer initiation, growth, and metastasis by increasing levels of ERK1 and 2.

Oncotarget. 2016 Aug 16;7(33):53853-53868

Authors: Ho JY, Hsu RJ, Wu CH, Liao GS, Gao HW, Wang TH, Yu CP

Abstract
Hyperactivation of the Ras/ERK pathway contributes to breast cancer initiation and progression, and recent evidence suggests aberrant signaling of miRNAs that regulate the Ras/ERK pathway play important roles during carcinogenesis and cancer progression. In this study, we demonstrate that miR-550a-3p expression is negatively correlated with levels of ERK1 and ERK2, two pivotal effectors in the Ras/ERK pathway. MiR-550a-3p gradually decreased during breast cancer initiation and progression and this reduction was a prognostic indicator of poorer overall survival (OS) and disease-free survival (DFS) among breast cancer patients. Our mechanistic studies demonstrated that miR-550a-3p exerts its tumor-suppressor role by directly repressing ERK1 and ERK2 protein expression, thereby suppressing the oncogenic ERK/RSK cascades, which reduced breast cancer cell viability, survival, migration, invasion, tumorigenesis, and metastasis. The inhibitory effects of miR-550a-3p were rescued by ectopic expression of ERK1 and/or ERK2. The novel connection between miR-550a-3p and ERK defines a new diagnostic and prognostic role for miR-550a-3p and highlights ERK inhibition as a candidate therapeutic target for breast cancers exhibiting hyperactivated Ras/ERK signaling.

PMID: 27462780 [PubMed - indexed for MEDLINE]

Standard PREanalytical Code version 3.0.

Tue, 01/30/2018 - 14:04

Standard PREanalytical Code version 3.0.

Biopreserv Biobank. 2018 Jan 29;:

Authors: Betsou F, Bilbao R, Case J, Chuaqui R, Clements JA, De Souza Y, De Wilde A, Geiger J, Grizzle W, Guadagni F, Gunter E, Heil S, Kiehntopf M, Koppandi I, Lehmann S, Linsen L, Mackenzie-Dodds J, Aguilar Quesada R, Tebbakha R, Selander T, Shea K, Sobel M, Somiari S, Spyropoulos D, Stone M, Tybring G, Valyi-Nagy K, Wadhwa L

PMID: 29377712 [PubMed - as supplied by publisher]

Planning Today for Tomorrow's Research: Analysis of Factors Influencing Participation in a Pediatric Cancer Research Biorepository.

Tue, 01/30/2018 - 14:04
Related Articles

Planning Today for Tomorrow's Research: Analysis of Factors Influencing Participation in a Pediatric Cancer Research Biorepository.

Front Oncol. 2017;7:324

Authors: Labib RM, Hassanain O, Alaa M, Ahmed S, Abou El-Naga S

Abstract
Background: Biobanks have become a powerful tool that fosters biomedical research. The success of biobanks depends upon people's perception and willingness to donate their samples for research. This is the first biorepository in Egypt, hence, little is known about the beliefs and attitudes of parents toward participation.
Aim: To investigate the level of willingness of Egyptians to donate samples of their children and themselves for research and the different factors influencing participation.
Materials and methods: A structured questionnaire was designed covering multiple items expected to affect the enrollment decision. This was conducted in-person, and data collected included demographic data, socioeconomic, and educational level. In addition, in the case of refusal, participants were asked about reasons behind their decision.
Results: Only about 3.1% of patients have not been enrolled in the project, and 0.3% have withdrawn. Three demographic factors were found having disparate trends in the decision-making process to participate or not: father's education (p = 0.0001), mother's education (p = 0.0001), and father's age (p = 0.034).
Conclusion: Egyptian parents were willing to donate their samples as well as their children's samples in our research biorepository. The idea of participation was presented in an interview during which the consent form was explained in a comprehensive transparent way allowing participants the right to refuse or withdraw at any time. Still, different communication approaches are needed with older, more highly educated parents to encourage them to participate.

PMID: 29376026 [PubMed]

Growth Hormone, Insulin-Like Growth Factor-1, Insulin Resistance, and Leukocyte Telomere Length as Determinants of Arterial Aging in Subjects Free of Cardiovascular Diseases.

Tue, 01/30/2018 - 14:04
Related Articles

Growth Hormone, Insulin-Like Growth Factor-1, Insulin Resistance, and Leukocyte Telomere Length as Determinants of Arterial Aging in Subjects Free of Cardiovascular Diseases.

Front Genet. 2017;8:198

Authors: Strazhesko ID, Tkacheva ON, Akasheva DU, Dudinskaya EN, Plokhova EV, Pykhtina VS, Kruglikova AS, Brailova NV, Sharashkina NV, Kashtanova DA, Isaykina OY, Pokrovskaya MS, Vygodin VA, Ozerova IN, Skvortsov DA, Boytsov SA

Abstract
Background: Increased arterial stiffness (AS), intima-media thickness (IMT), and the presence of atherosclerotic plaques (PP) have been considered as important aspects of vascular aging. It is well documented that the cardiovascular system is an important target organ for growth hormone (GH) and insulin-like growth factor (IGF)-1 in humans, and GH /IGF-1 deficiency significantly increases the risk for cardiovascular diseases (CVD). The telomere length of peripheral blood leukocytes (LTL) is a biomarker of cellular senescence and that has been proposed as an independent predictor of (CVD). The aim of this study is to determine the role of GH/IGF-1, LTL and their interaction cardiovascular risk factors (CVRF) in the vascular aging. Methods: The study group included 303 ambulatory participants free of known CVD (104 males and 199 females) with a mean age of 51.8 ± 13.3 years. All subjects had one or more CVRF [age, smoking, arterial hypertension, obesity, dyslipidemia, fasting hyperglycemia, insulin resistance-HOMA (homeostatic model assessment) >2.5, or high glycated hemoglobin]. The study sample was divided into the two groups according to age as "younger" (m ≤ 45 years, f ≤ 55 years) and "older" (m > 45 years, f > 55 years). IMT and PP were determined by ultrasonography, AS was determined by measuring the carotid-femoral pulse wave velocity (c-f PWV) using the SphygmoCor system (AtCor Medical). LTL was determined by PCR. Serum IGF-1 and GH concentrations we measured by immunochemiluminescence analysis. Results: Multiple linear regression analysis with adjustment for CVRF indicated that HOMA, GH, IGF-1, and LTL had an independent relationship with all the arterial wall parameters investigated in the younger group. In the model with c-f PWV as a dependent variable, p < 0.001 for HOMA, p = 0.03 for GH, and p = 0.004 for LTL. In the model with IMT as a dependent variable, p = 0.0001 for HOMA, p = 0.044 for GH, and p = 0.004 for IGF-1. In the model with the number of plaques as a dependent variable, p = 0.0001 for HOMA, and p = 0.045 for IGF-1. In the older group, there were no independent significant associations between GH/IGF-1, LTL, HOMA, and arterial wall characteristics. Conclusions: GH/IGF-1, IR, HOMA, and LTL were the important parameters of arterial aging in younger healthy participants.

PMID: 29375617 [PubMed]

[Sex-specific associations between tobacco smoking and risk of cardiovascular diseases in Chinese adults].

Tue, 01/30/2018 - 14:04
Related Articles

[Sex-specific associations between tobacco smoking and risk of cardiovascular diseases in Chinese adults].

Zhonghua Liu Xing Bing Xue Za Zhi. 2018 Jan 10;39(1):8-15

Authors: Shen Q, Zhu NB, Yu CQ, Guo Y, Bian Z, Tan YL, Pei P, Chen JS, Chen ZM, Lyu J, Li LM, China Kadoorie Biobank (CKB) Collaborative Group

Abstract
Objective: To examine the sex-specific associations between tobacco smoking and risk of cardiovascular diseases in Chinese adults. Methods: The present analysis included 487 373 participants from the China Kadoorie Biobank after excluding those with cancer, heart diseases, stroke at baseline survey. The baseline survey was conducted from June 2004 to July 2008. The number of follow-up years was calculated from the time that the participants completed baseline survey to the time of any event: CVD incidence, death, loss of follow-up, or December 31, 2015, whichever occurred first. We used Cox proportional hazards regression models to estimate the HRs and 95%CI of incident cardiovascular diseases with tobacco smoking. Results: During a median follow-up of 8.9 years(a total of 4.1 million person years), we documented 33 947 cases of ischemic heart diseases, 6 048 cases of major coronary diseases, 7 794 cases of intracerebral hemorrhage, and 31 722 cases of cerebral infarction. The prevalence of smoking was much higher in men (67.9%) than in women (2.7%). Smoking increased risk of all subtypes of cardiovascular diseases. Compared with nonsmokers, the multivariable-adjusted HRs (95% CI) for current smokers were 1.54 (1.43-1.66) for major coronary event, 1.28 (1.24-1.32) for ischemic heart disease, 1.18 (1.14-1.22) for cerebral infarction, and 1.07 (1.00-1.15) for intracerebral hemorrhage, respectively. Female smokers tended to have greater risk of developing major coronary event associated with amount of tobacco smoked daily (interaction P=0.006) and age when smoking started (interaction P=0.011). There was no sex difference in these two effects for ischemic heart diseases, intracerebral hemorrhage and cerebral infarction (all interaction P>0.05). Conclusions: This prospective study confirmed increased risk of all subtypes of cardiovascular diseases in current smokers. Smoking was more harmful to women than to men for major coronary event.

PMID: 29374887 [PubMed - in process]

Tumor immune microenvironment and nivolumab efficacy in EGFR mutation-positive non-small-cell lung cancer based on T790M status after disease progression during EGFR-TKI treatment.

Tue, 01/30/2018 - 14:04
Related Articles

Tumor immune microenvironment and nivolumab efficacy in EGFR mutation-positive non-small-cell lung cancer based on T790M status after disease progression during EGFR-TKI treatment.

Ann Oncol. 2017 Jul 01;28(7):1532-1539

Authors: Haratani K, Hayashi H, Tanaka T, Kaneda H, Togashi Y, Sakai K, Hayashi K, Tomida S, Chiba Y, Yonesaka K, Nonagase Y, Takahama T, Tanizaki J, Tanaka K, Yoshida T, Tanimura K, Takeda M, Yoshioka H, Ishida T, Mitsudomi T, Nishio K, Nakagawa K

Abstract
Background: The efficacy of programmed death-1 blockade in epidermal growth factor receptor gene (EGFR) mutation-positive non-small-cell lung cancer (NSCLC) patients with different mechanisms of acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) is unknown. We retrospectively evaluated nivolumab efficacy and immune-related factors in such patients according to their status for the T790M resistance mutation of EGFR.
Patients and methods: We identified 25 patients with EGFR mutation-positive NSCLC who were treated with nivolumab after disease progression during EGFR-TKI treatment (cohort A). Programmed death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocyte (TIL) density in tumor specimens obtained after acquisition of EGFR-TKI resistance were determined by immunohistochemistry. Whole-exome sequencing of tumor DNA was carried out to identify gene alterations. The relation of T790M status to PD-L1 expression or TIL density was also examined in an independent cohort of 60 patients (cohort B).
Results: In cohort A, median progression-free survival (PFS) was 2.1 and 1.3 months for T790M-negative and T790M-positive patients, respectively (P = 0.099; hazard ratio of 0.48 with a 95% confidence interval of 0.20-1.24). Median PFS was 2.1 and 1.3 months for patients with a PD-L1 expression level of ≥1% or <1%, respectively (P = 0.084; hazard ratio of 0.37, 95% confidence interval of 0.10-1.21). PFS tended to increase as the PD-L1 expression level increased with cutoff values of ≥10% and ≥50%. The proportion of tumors with a PD-L1 level of ≥10% or ≥50% was higher among T790M-negative patients than among T790M-positive patients of both cohorts A and B. Nivolumab responders had a significantly higher CD8+ TIL density and nonsynonymous mutation burden.
Conclusion: T790M-negative patients with EGFR mutation-positive NSCLC are more likely to benefit from nivolumab after EGFR-TKI treatment, possibly as a result of a higher PD-L1 expression level, than are T790M-positive patients.

PMID: 28407039 [PubMed - indexed for MEDLINE]

Diagnosis of HPV driven oropharyngeal cancers: Comparing p16 based algorithms with the RNAscope HPV-test.

Tue, 01/30/2018 - 14:04
Related Articles

Diagnosis of HPV driven oropharyngeal cancers: Comparing p16 based algorithms with the RNAscope HPV-test.

Oral Oncol. 2016 Nov;62:101-108

Authors: Mirghani H, Casiraghi O, Guerlain J, Amen F, He MX, Ma XJ, Luo Y, Mourareau C, Drusch F, Lakdhar AB, Melkane A, St Guily L, Badoual C, Scoazec JY, Borget I, Aupérin A, Dalstein V, Vielh P

Abstract
BACKGROUND: Accurate identification of HPV-driven oropharyngeal cancer (OPC) is a major issue and none of the current diagnostic approaches is ideal. An in situ hybridization (ISH) assay that detects high-risk HPV E6/E7 mRNA, called the RNAscope HPV-test, has been recently developed. Studies have suggested that this assay may become a standard to define HPV-status.
METHODS: To further assess this test, we compared its performance against the strategies that are used in routine clinical practice: p16 immunohistochemistry (IHC) as a single test and algorithms combining p16-IHC with HPV-DNA identification by PCR (algorithm-1) or ISH (algorithm-2).
RESULTS: 105 OPC specimens were analyzed. The prevalence of HPV-positive samples varied considerably: 67% for p16-IHC, 54% for algorithm-1, 61% for algorithm-2 and 59% for the RNAscope HPV-test. Discrepancies between the RNAscope HPV-test and p16-IHC, algorithm-1 and 2 were noted in respectively 13.3%, 13.1%, and 8.6%. The 4 diagnostic strategies were able to identify 2 groups with different prognosis according to HPV-status, as expected. However, the greater survival differential was observed with the RNAscope HPV-test [HR: 0.19, 95% confidence interval (CI), 0.07-0.51, p=0.001] closely followed by algorithm-1 (HR: 0.23, 95% CI, 0.08-0.66, p=0.006) and algorithm-2 (HR: 0.26, 95% CI, 0.1-0.65, p=0.004). In contrast, a weaker association was found when p16-IHC was used as a single test (HR: 0.33, 95% CI, 0.13-0.81, p=0.02).
CONCLUSIONS: Our findings suggest that the RNAscope HPV-test and p16-based algorithms perform better that p16 alone to identify OPC that are truly driven by HPV-infection. The RNAscope HPV-test has the advantage of being a single test.

PMID: 27865361 [PubMed - indexed for MEDLINE]

Cerebrospinal Fluid Alzheimer's Disease Biomarkers Across the Spectrum of Lewy Body Diseases: Results from a Large Multicenter Cohort.

Tue, 01/30/2018 - 14:04
Related Articles

Cerebrospinal Fluid Alzheimer's Disease Biomarkers Across the Spectrum of Lewy Body Diseases: Results from a Large Multicenter Cohort.

J Alzheimers Dis. 2016 Aug 18;54(1):287-95

Authors: van Steenoven I, Aarsland D, Weintraub D, Londos E, Blanc F, van der Flier WM, Teunissen CE, Mollenhauer B, Fladby T, Kramberger MG, Bonanni L, Lemstra AW, European DLB consortium

Abstract
BACKGROUND: Concomitant Alzheimer's disease (AD) pathology is observed in Lewy body diseases (LBD), but the clinical impact is unknown. Only a few biomarker studies in LBD exist and have included small cohorts from single centers.
OBJECTIVE: We aimed to evaluate the prevalence of abnormal cerebrospinal fluid (CSF) AD biomarkers across the spectrum of LBD in a large multicenter cohort and to assess whether an AD biomarker profile was associated with demographic and clinical differences in dementia with Lewy bodies (DLB).
METHODS: We included 375 DLB patients, 164 Parkinson's disease (PD) patients without dementia, and 55 PD patients with dementia (PDD) from 10 centers. CSF amyloid-beta42 (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau) values were dichotomized as abnormal or normal according to locally available cut-off values. A CSF AD profile was defined as abnormal Aβ42 combined with abnormal t-tau and/or p-tau.
RESULTS: A substantial proportion of DLB patients had abnormal values for CSF Aβ42, t-tau, and p-tau, while abnormal values were uncommon in PD without dementia. Patients with PDD had values in between. A CSF AD profile was observed in 25% of DLB patients, compared with only 9% of PDD and 3% of PD without dementia. Within DLB, patients with a CSF AD profile were older, more often female, performed worse on the Mini-Mental State Examination, and had shorter disease duration compared with patients with normal CSF.
CONCLUSION: A CSF AD profile is more common in DLB compared with PDD and PD, and is associated with more severe cognitive impairment in DLB.

PMID: 27567832 [PubMed - indexed for MEDLINE]

A Decade of Cerebrospinal Fluid Biomarkers for Alzheimer's Disease in Belgium.

Tue, 01/30/2018 - 14:04
Related Articles

A Decade of Cerebrospinal Fluid Biomarkers for Alzheimer's Disease in Belgium.

J Alzheimers Dis. 2016 Aug 10;54(1):383-95

Authors: Somers C, Struyfs H, Goossens J, Niemantsverdriet E, Luyckx J, De Roeck N, De Roeck E, De Vil B, Cras P, Martin JJ, De Deyn PP, Bjerke M, Engelborghs S

Abstract
During the past ten years, over 5,000 cerebrospinal fluid (CSF) samples were analyzed at the Reference Center for Biological Markers of Dementia (BIODEM), UAntwerp, for core Alzheimer's disease (AD) CSF biomarkers: amyloid-β peptide of 42 amino acids (Aβ1-42), total tau protein (T-tau), and tau phosphorylated at threonine 181 (P-tau181P). CSF biomarker analyses were performed using single-analyte ELISA kits. In-house validated cutoff values were applied: Aβ1-42 <638.5 pg/mL, T-tau >296.5 pg/mL, P-tau181P >56.5 pg/mL. A CSF biomarker profile was considered to be suggestive for AD if the CSF Aβ1-42 concentration was below the cutoff, in combination with T-tau and/or P-tau181P values above the cutoff (IWG2 criteria for AD). Biomarker analyses were requested for following clinical indications: 1) neurochemical confirmation of AD in case of clinical AD, 2) neurochemical confirmation of AD in case of doubt between AD and a non-AD dementia, 3) neurochemical diagnosis of prodromal AD in case of mild cognitive impairment, 4) neurochemical confirmation of AD in case of psychiatric symptoms (like depression, psychosis), or 5) other clinical indications. During these ten years, the number of yearly referred samples increased by 238% and clinical indications for referral showed a shift from neurochemical confirmation of AD in case of clinical AD to differential dementia diagnosis in case of doubt between AD and a non-AD dementia. Four percent of the patients also had a postmortem neuropathological examination. Together, these biomarker data were the basis for several research papers, and significantly contributed to the validation of these biomarkers in autopsy-confirmed subjects.

PMID: 27567807 [PubMed - indexed for MEDLINE]