Biobank publications

Subscribe to Biobank publications feed Biobank publications
NCBI: db=pubmed; Term=biobank
Updated: 1 hour 30 min ago

How to deal with uveitis patients?

Sat, 02/10/2018 - 13:46

How to deal with uveitis patients?

Curr Mol Med. 2018 Feb 07;:

Authors: Yang P, Du L, Ye Z

Abstract
During the past nine years, our center has grown into the largest uveitis referral center in China. To deal with this increasing stream of patients we have developed a management system to coordinate communication with our patients, their referring ophthalmologists, consultations with other medical specialties and world-renowned foreign uveitis specialists. Tools have been developed to deal with patient records, which include a patient database allowing continuous analysis of clinical features and response to treatment of patients with various uveitis entities as well as the evaluation of the relevance of various ancillary tests performed in this patient group. The establishment of a patient database and specimen biobank has been shown to be instrumental in the research on the complex immunopathological mechanisms involved in this disease. The close interaction between patient care and clinical research under one roof has led to a novel understanding of disease mechanisms and will undoubtedly lead to a tailored treatment for this disease.

PMID: 29424311 [PubMed - as supplied by publisher]

Integrating the dysregulated inflammasome-based molecular functionome in the malignant transformation of endometriosis-associated ovarian carcinoma.

Sat, 02/10/2018 - 13:46

Integrating the dysregulated inflammasome-based molecular functionome in the malignant transformation of endometriosis-associated ovarian carcinoma.

Oncotarget. 2018 Jan 09;9(3):3704-3726

Authors: Chang CM, Wang ML, Lu KH, Yang YP, Juang CM, Wang PH, Hsu RJ, Yu MH, Chang CC

Abstract
The coexistence of endometriosis (ES) with ovarian clear cell carcinoma (CCC) or endometrioid carcinoma (EC) suggested that malignant transformation of ES leads to endometriosis associated ovarian carcinoma (EAOC). However, there is still lack of an integrating data analysis of the accumulated experimental data to provide the evidence supporting the hypothesis of EAOC transformation. Herein we used a function-based analytic model with the publicly available microarray datasets to investigate the expression profiling between ES, CCC, and EC. We analyzed the functional regularity pattern of the three type of samples and hierarchically clustered the gene sets to identify key mechanisms regulating the malignant transformation of EAOC. We identified a list of 18 genes (NLRP3, AIM2, PYCARD, NAIP, Caspase-4, Caspase-7, Caspase-8, TLR1, TLR7, TOLLIP, NFKBIA, TNF, TNFAIP3, INFGR2, P2RX7, IL-1B, IL1RL1, IL-18) closely related to inflammasome complex, indicating an important role of inflammation/immunity in EAOC transformation. We next explore the association between these target genes and patient survival using Gene Expression Omnibus (GEO), and found significant correlation between the expression levels of the target genes and the progression-free survival. Interestingly, high expression levels of AIM2 and NLRP3, initiating proteins of inflammasomes, were significantly correlated with poor progression-free survival. Immunohistochemistry staining confirmed a correlation between high AIM2 and high Ki-67 in clinical EAOC samples, supporting its role in disease progression. Collectively, we established a bioinformatic platform of gene-set integrative molecular functionome to dissect the pathogenic pathways of EAOC, and demonstrated a key role of dysregulated inflammasome in modulating the malignant transformation of EAOC.

PMID: 29423077 [PubMed]

Combined effects of PLK1 and RAS in hepatocellular carcinoma reveal rigosertib as promising novel therapeutic "dual-hit" option.

Sat, 02/10/2018 - 13:46

Combined effects of PLK1 and RAS in hepatocellular carcinoma reveal rigosertib as promising novel therapeutic "dual-hit" option.

Oncotarget. 2018 Jan 09;9(3):3605-3618

Authors: Dietrich P, Freese K, Mahli A, Thasler WE, Hellerbrand C, Bosserhoff AK

Abstract
Inhibition of RAS-RAF-ERK-signaling is a major mechanism mediated by the multi-kinase inhibitors sorafenib and regorafenib, the only effective therapeutic approaches for advanced hepatocellular carcinoma (HCC). This underlines the importance of RAS-RAF-ERK-signaling in HCC. Most RAS isoforms were not yet described to play crucial roles in HCC. However, several studies indicate that the HRAS isoform can function as potent oncogene in HCC, but pharmacologic RAS inhibition has not yet been investigated. Moreover, the cell cycle promoting polo-like kinase 1 (PLK1) is an increasingly recognized therapeutic target in HCC that can be activated by RAS-RAF-signaling. A recently developed small molecule inhibitor, ON-01910 ("rigosertib", RGS), was shown to interfere with both RAS- and PLK1-signaling. The aim of this study was to analyze the effects of RGS in HCC and to assess PLK1 and HRAS expression in HCC. RGS treatment reduced cell proliferation and induced cell cycle arrest in human HCC cell lines in vitro. Moreover, RGS strongly inhibited both ERK- and AKT-activation in HCC cells, indicating disruption of RAS-signaling. Analysis of HCC patient data showed that PLK1 and HRAS expression levels are upregulated during HCC development and in advanced HCC, respectively. High expression levels of PLK1 significantly correlated with poor patient survival. Moreover, high expression of both PLK1 and HRAS revealed combined effects on patient outcome. This underscores the importance of these genes and associated pathways in HCC. We newly demonstrate the therapeutic potential of RGS in HCC by inhibition of both PLK1 activation and major RAS-pathways, revealing a novel therapeutic "dual-hit" approach for HCC.

PMID: 29423069 [PubMed]

Individual and combined effect of TP53, MDM2, MDM4, MTHFR, CCR5, and CASP8 gene polymorphisms in lung cancer.

Sat, 02/10/2018 - 13:46

Individual and combined effect of TP53, MDM2, MDM4, MTHFR, CCR5, and CASP8 gene polymorphisms in lung cancer.

Oncotarget. 2018 Jan 09;9(3):3214-3229

Authors: Stumbryte A, Gudleviciene Z, Kundrotas G, Dabkeviciene D, Kunickaite A, Cicenas S

Abstract
Lung cancer (LC) is the second common and with the highest mortality oncological disease. Specific biomarkers for its diagnostics, treatment, and prognosis are still under the investigations. Aim of our study was to evaluate the relationship between the polymorphisms of TP53 pathway genes TP53, MDM2, MDM4, the polymorphisms of HPV-associated genes MTHFR, CASP8, CCR5, and HPV infection with survival of LC patients. SNPs were genotyped using PCR-RFLP. qRT-PCR was used to detect, identify, and quantify HPV. No statistically significant differences were detected between individual SNPs and patient survival with stage I-IV LC. Cluster analysis of SNPs in genes MDM4 A/A, CCR5 wt/Δ32, MTHFR C/T, MDM2 T/T showed possible association with the worse survival. Patients who were diagnosed with C/T polymorphic variant of gene MTHFR tend not to survive stage III-IV LC (P = .12). There is a tendency between MDM2 gene T/T variant and worse survival of patients diagnosed with late stage LC (P = .11). HPV infection is very rear among LC patients (3 of 92). Overall, there is a link, although statistically insignificant, between specific SNPs and LC patient survival frequency and time, meanwhile the combination of specific SNPs showed a statistically significant measure. In conclusion, we determined statistically significant (P = .04) link between the poor survival of LC patients after surgery and the combination of polymorphic variants C/T of the MTHFR and T/T of the MDM2 genes, whereas individually these SNPs do not show significant relationship with the survival of patients after surgery.

PMID: 29423041 [PubMed]

New CSF biomarkers on the block.

Sat, 02/10/2018 - 13:46
Related Articles

New CSF biomarkers on the block.

EMBO Mol Med. 2016 10;8(10):1118-1119

Authors: Teunissen CE, Parnetti L

PMID: 27621274 [PubMed - indexed for MEDLINE]

On metabolic reprogramming and tumor biology: A comprehensive survey of metabolism in breast cancer.

Sat, 02/10/2018 - 13:46
Related Articles

On metabolic reprogramming and tumor biology: A comprehensive survey of metabolism in breast cancer.

Oncotarget. 2016 Oct 11;7(41):67626-67649

Authors: Penkert J, Ripperger T, Schieck M, Schlegelberger B, Steinemann D, Illig T

Abstract
Altered metabolism in tumor cells has been a focus of cancer research for as long as a century but has remained controversial and vague due to an inhomogeneous overall picture. Accumulating genomic, metabolomic, and lastly panomic data as well as bioenergetics studies of the past few years enable a more comprehensive, systems-biologic approach promoting deeper insight into tumor biology and challenging hitherto existing models of cancer bioenergetics. Presenting a compendium on breast cancer-specific metabolome analyses performed thus far, we review and compile currently known aspects of breast cancer biology into a comprehensive network, elucidating previously dissonant issues of cancer metabolism. As such, some of the aspects critically discussed in this review include the dynamic interplay or metabolic coupling between cancer (stem) cells and cancer-associated fibroblasts, the intratumoral and intertumoral heterogeneity and plasticity of cancer cell metabolism, the existence of distinct metabolic tumor compartments in need of separate yet simultaneous therapeutic targeting, the reliance of cancer cells on oxidative metabolism and mitochondrial power, and the role of pro-inflammatory, pro-tumorigenic stromal conditioning. Comprising complex breast cancer signaling networks as well as combined metabolomic and genomic data, we address metabolic consequences of mutations in tumor suppressor genes and evaluate their contribution to breast cancer predisposition in a germline setting, reasoning for distinct personalized preventive and therapeutic measures. The review closes with a discussion on central root mechanisms of tumor cell metabolism and rate-limiting steps thereof, introducing essential strategies for therapeutic targeting.

PMID: 27590516 [PubMed - indexed for MEDLINE]

Epidermal lipid composition, barrier integrity and eczematous inflammation are associated with skin microbiome configuration.

Fri, 02/09/2018 - 14:58

Epidermal lipid composition, barrier integrity and eczematous inflammation are associated with skin microbiome configuration.

J Allergy Clin Immunol. 2018 Feb 05;:

Authors: Baurecht H, Rühlemann MC, Rodríguez E, Thielking F, Harder I, Erkens AS, Stölzl D, Ellinghaus E, Hotze M, Lieb W, Wang S, Heinsen FA, Franke A, Weidinger S

Abstract
BACKGROUND: Genomic approaches have revealed characteristic site-specificities of skin bacterial community structures. In addition, in children with atopic dermatitis (AD), characteristic shifts were described at creases and in particular during flares, which have been postulated to mirror the disturbed skin barrier function and/or cutaneous inflammation.
OBJECTIVE: We sought to comprehensively analyse microbial configurations in AD across body sites, and to explore the impact of distinct abnormalities of epidermal barrier function.
METHODS: The skin microbiome was determined by bacterial 16S rRNA sequencing at 4 nonlesional body sites as well as acute and chronic lesions of 10 AD patients and 10 healthy controls matched for age, sex and FLG mutation status. Nonlesional sampling sites were characterized for skin physiology parameters including chromatography-based lipid profiling.
RESULTS: Epidermal lipid composition, in particular levels of long-chain unsaturated free fatty acids, strongly correlated with bacterial composition, in particular Propionibacteria and Corynebacteria abundance. AD displayed a distinct community structure with increased abundance and altered composition of staphylococcal species across body sites with the strongest loss of diversity and increase of S. aureus seen on chronic lesions, and a progressive shift from nonlesional skin to acute and chronic lesions. FLG deficient skin showed a distinct microbiome composition partly resembling the AD-related pattern.
CONCLUSION: Epidermal barrier integrity and function impact the skin microbiome composition. AD shows an altered microbial configuration across diverse body sites, which however is most pronounced at sites of predilection and atopic dermatitis. Eczematous affection appears to be a more important determinant than body site.

PMID: 29421277 [PubMed - as supplied by publisher]

Lipids, Lipoproteins, and Metabolites and Risk of Myocardial Infarction and Stroke.

Fri, 02/09/2018 - 14:58

Lipids, Lipoproteins, and Metabolites and Risk of Myocardial Infarction and Stroke.

J Am Coll Cardiol. 2018 Feb 13;71(6):620-632

Authors: Holmes MV, Millwood IY, Kartsonaki C, Hill MR, Bennett DA, Boxall R, Guo Y, Xu X, Bian Z, Hu R, Walters RG, Chen J, Ala-Korpela M, Parish S, Clarke RJ, Peto R, Collins R, Li L, Chen Z, China Kadoorie Biobank Collaborative Group

Abstract
BACKGROUND: Blood lipids are established risk factors for myocardial infarction (MI), but uncertainty persists about the relevance of lipids, lipoprotein particles, and circulating metabolites for MI and stroke subtypes.
OBJECTIVES: This study sought to investigate the associations of plasma metabolic markers with risks of incident MI, ischemic stroke (IS), and intracerebral hemorrhage (ICH).
METHODS: In a nested case-control study (912 MI, 1,146 IS, and 1,138 ICH cases, and 1,466 common control subjects) 30 to 79 years of age in China Kadoorie Biobank, nuclear magnetic resonance spectroscopy measured 225 metabolic markers in baseline plasma samples. Logistic regression was used to estimate adjusted odds ratios (ORs) for a 1-SD higher metabolic marker.
RESULTS: Very low-, intermediate-, and low-density lipoprotein particles were positively associated with MI and IS. High-density lipoprotein (HDL) particles were inversely associated with MI apart from small HDL. In contrast, no lipoprotein particles were associated with ICH. Cholesterol in large HDL was inversely associated with MI and IS (OR: 0.79 and 0.88, respectively), whereas cholesterol in small HDL was not (OR: 0.99 and 1.06, respectively). Triglycerides within all lipoproteins, including most HDL particles, were positively associated with MI, with a similar pattern for IS. Glycoprotein acetyls, ketone bodies, glucose, and docosahexaenoic acid were associated with all 3 diseases. The 225 metabolic markers showed concordant associations between MI and IS, but not with ICH.
CONCLUSIONS: Lipoproteins and lipids showed similar associations with MI and IS, but not with ICH. Within HDL particles, cholesterol concentrations were inversely associated, whereas triglyceride concentrations were positively associated with MI. Glycoprotein acetyls and several non-lipid-related metabolites associated with all 3 diseases.

PMID: 29420958 [PubMed - in process]

Significance of cyclin D1 overexpression in progression and radio-resistance of pediatric ependymomas.

Fri, 02/09/2018 - 14:58

Significance of cyclin D1 overexpression in progression and radio-resistance of pediatric ependymomas.

Oncotarget. 2018 Jan 05;9(2):2527-2542

Authors: Liang ML, Hsieh TH, Liu YR, Chen YW, Lee YY, Chang FC, Lin SC, Huang MC, Donald Ming-Tak H, Wong TT, Yen Y, Yang MH

Abstract
Due to the limited efficacy of chemotherapy, the applications of adjuvant irradiation play an important role for ependymoma treatment. However, in the young ages, the resistance of residual and recurrent tumor, and long-term intellectual sequelae remain the major obstacles of radiotherapy. Understanding the mechanism of therapeutic failure caused by radio-resistance is, therefore, crucial in ependymoma treatment. Here we retrospectively analyze clinic-pathological factors in 82 cases of ependymoma less than 20 years old and identify radio-resistant genes through gene expression microarray followed by qRT-PCR validation and immunohistochemistry staining. Thirty-one out of 82 (37.8%) patients are under 3-year-old. The 10 years PFS and OS are 38% and 60%. Gross-total resection is the single significant prognostic factor for longer 10 years PFS and OS in the multivariant analysis (p<0.05). According to the microarray analysis, CCND1 is up-regulated in supratentorial and infratentorial ependymomas and is associated with DNA repair. We demonstrated that 24 primary and 16 recurrent ependymomas were up-regulated, and 5 out of 7 paired samples exhibited higher CCND1 expression in recurrent tumors. We also found RAD51, another DNA repair gene, was up-regulated in supratentorial and infratentorial ependymomas. Knocking down CCND1 reduced cell proliferation and repressed several genes associated with S-phase and DNA repair. Homologous recombination activities of DNA repair were significantly decreased in CCND1-deficient cells while the level of γH2AX was increased after irradiation. In summary, these observations suggest a robust role of CCND1 in regulating cell proliferation and radio-resistance in ependymomas, providing a potential therapeutic target for pediatric ependymomas.

PMID: 29416789 [PubMed]

Increased risk of Parkinson's disease following tension-type headache: a nationwide population-based cohort study.

Fri, 02/09/2018 - 14:58

Increased risk of Parkinson's disease following tension-type headache: a nationwide population-based cohort study.

Oncotarget. 2018 Jan 05;9(2):2148-2157

Authors: Yang FC, Chen HJ, Lee JT, Chen SJ, Sung YF, Kao CH, Yang TY

Abstract
Purpose: Previous studies have suggested associations between primary headache and neurodegenerative diseases; however, the relationship between tension-type headache (TTH), which is the most common type of primary headache, and Parkinson's disease (PD) remains controversial. Hence, in this nationwide, population-based, retrospective cohort study, we explored the temporal association between TTH and PD.
Methods: Using claims data in the National Health Insurance Research Database of Taiwan, we evaluated 12,309 subjects aged ≥20 years who were newly diagnosed with TTH from 2000 to 2005. The non-TTH group included 49,236 randomly selected sex- and age-matched patients without TTH. Subjects were followed up until the end of 2011, diagnosis of PD, or death. The incidence of PD was compared between the two groups. A Cox multivariable proportional hazards model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) to estimate the risk of PD.
Results: The overall incidence of PD (per 1,000 person-years) in the TTH and non-TTH groups was 3.01 and 1.68, respectively. After adjustment for sex, age, and comorbidities, the association between TTH and PD remained statistically significant (adjusted HR = 1.37, 95% CI = 1.19-1.57). The TTH group had a higher risk of PD than the non-TTH group did, regardless of subjects' sex, age, and comorbidity status.
Conclusions: These findings demonstrate that patients diagnosed with TTH exhibit an increased risk of PD. Additional studies should investigate the potential shared pathophysiological mechanisms of TTH and PD. Clinicians should be aware that TTH is a potential risk factor for PD.

PMID: 29416761 [PubMed]

Relationship between CCR5(WT/Δ32) heterozygosity and HIV-1 reservoir size in adolescents and young adults with perinatally acquired HIV-1 infection.

Fri, 02/09/2018 - 14:58
Related Articles

Relationship between CCR5(WT/Δ32) heterozygosity and HIV-1 reservoir size in adolescents and young adults with perinatally acquired HIV-1 infection.

Clin Microbiol Infect. 2017 May;23(5):318-324

Authors: Martínez-Bonet M, González-Serna A, Clemente MI, Morón-López S, Díaz L, Navarro M, Puertas MC, Leal M, Ruiz-Mateos E, Martinez-Picado J, Muñoz-Fernández MA

Abstract
BACKGROUND: Several host factors contribute to human immunodeficiency virus (HIV) disease progression in the absence of combination antiretroviral therapy (cART). Among them, the CC-chemokine receptor 5 (CCR5) is known to be the main co-receptor used by HIV-1 to enter target cells during the early stages of an HIV-1 infection.
OBJECTIVE: We evaluated the association of CCR5(WT/Δ32) heterozygosity with HIV-1 reservoir size, lymphocyte differentiation, activation and immunosenescence in adolescents and young adults with perinatally acquired HIV infection receiving cART.
METHODS: CCR5 genotype was analysed in 242 patients with vertically transmitted HIV-1 infection from Paediatric Spanish AIDS Research Network Cohort (coRISpe). Proviral HIV-1 DNA was quantified by digital-droplet PCR, and T-cell phenotype was evaluated by flow cytometry in a subset of 24 patients (ten with CCR5(Δ32/WT) genotype and 14 with CCR5(WT/WT) genotype).
RESULTS: Twenty-three patients were heterozygous for the Δ32 genotype but none was homozygous for the mutated CCR5 allele. We observed no difference in the HIV-1 reservoir size (455 and 578 copies of HIV-1 DNA per million CD4+ T cells in individuals with CCR5(WT/WT) and CCR5(Δ32/WT) genotypes, respectively; p 0.75) or in the immune activation markers between both genotype groups. However, we found that total HIV-1 DNA in CD4+ T cells correlated with the percentage of memory CD4+ T cells: a direct correlation in CCR5(WT/Δ32) patients but an inverse correlation in those with the CCR5(WT/WT) genotype.
CONCLUSIONS: This finding suggests a differential distribution of the viral reservoir compartment in CCR5(WT/Δ32) patients with perinatal HIV infection, which is a characteristic that may affect the design of strategies for reservoir elimination.

PMID: 28042001 [PubMed - indexed for MEDLINE]

Biospecimens and Biobanking in Global Health.

Thu, 02/08/2018 - 12:53

Biospecimens and Biobanking in Global Health.

Clin Lab Med. 2018 Mar;38(1):183-207

Authors: Mendy M, Lawlor RT, van Kappel AL, Riegman PHJ, Betsou F, Cohen OD, Henderson MK

Abstract
Biobanks provide a critical infrastructure to support research in human health. Biospecimens and their accompanying data are increasingly needed to support biomedical research and clinical care. The original text was initially published in the Handbook for Cancer Research in Africa. The value of this publication is great as it underlines the importance of biobanks in Africa as a key resource to increase quality scientific research and participate in global health research. Therefore, a revision to extend these principles to other low resource contexts, to include updated material and references and add the topic of biobank sustainability were relevant.

PMID: 29412882 [PubMed - in process]

Use of the 22C3 anti-programmed death ligand 1 antibody to determine programmed death ligand 1 expression in cytology samples obtained from non-small cell lung cancer patients.

Thu, 02/08/2018 - 12:53

Use of the 22C3 anti-programmed death ligand 1 antibody to determine programmed death ligand 1 expression in cytology samples obtained from non-small cell lung cancer patients.

Cancer Cytopathol. 2018 Feb 07;:

Authors: Ilie M, Juco J, Huang L, Hofman V, Khambata-Ford S, Hofman P

Abstract
BACKGROUND: Pembrolizumab monotherapy is a standard-of-care treatment for the first- and second-line treatment of advanced non-small cell lung cancer with programmed death ligand 1 (PD-L1) tumor proportion score (TPS) values ≥ 50% and ≥ 1%, respectively. PD-L1 testing with the PD-L1 immunohistochemistry (IHC) 22C3 pharmDx companion assay has been validated on tumor tissue with the Dako Autostainer Link 48 (ASL48). 22C3 anti-PD-L1 antibody-based laboratory-developed tests (LDTs) compatible with other autostainers and cytology samples are essential to support pembrolizumab treatment decisions across institutions globally.
METHODS: ASL48 and BenchMark Ultra LDTs were optimized for the evaluation of cytology samples through comparisons with cell lines with known PD-L1 expression levels (strong, moderate, and negative). The PD-L1 TPS was then evaluated for 70 paired biopsy and cytology samples (bronchial washes, n = 40; pleural effusions, n = 30) with these LDTs. Biopsy and cytology LDT TPS values were also compared with a subset of biopsy samples (n = 37) evaluated with the PD-L1 IHC 22C3 pharmDx assay on the ASL48.
RESULTS: Intraclass correlation coefficients of 0.884 to 0.898 were observed for biopsy samples versus cytology samples with the ASL48 and BenchMark Ultra LDTs. Concordance was high, regardless of the TPS cut point (<1% vs ≥ 1% and <50% vs ≥ 50%), sample type (pleural effusion vs bronchial wash), or tumor histology (adenocarcinoma vs squamous cell carcinoma). Concordance was high for each LDT versus the PD-L1 IHC 22C3 pharmDx assay.
CONCLUSIONS: ALS48 and BenchMark Ultra 22C3 antibody concentrate-based LDTs have been validated for PD-L1 testing in cytology samples, and they will support reliable, high-quality PD-L1 testing across regions globally. Cancer Cytopathol 2018. © 2018 American Cancer Society.

PMID: 29411536 [PubMed - as supplied by publisher]

Circulating Neutrophil Counts Decrease in Response to Mitigated Air Quality in Stable COPD Patients.

Thu, 02/08/2018 - 12:53

Circulating Neutrophil Counts Decrease in Response to Mitigated Air Quality in Stable COPD Patients.

Biomed Environ Sci. 2018 Jan;31(1):66-71

Authors: Zhang ZL, Wang J, Liu F, Ding MJ, Liu F, Chen SF, Lu WJ

Abstract
This three-year study, based on the Guangzhou Institute of Respiratory Disease (GRID), chronic obstructive pulmonary disease (COPD) Biobank, was conducted in 36 COPD patients to estimate whether changes in levels of leukocytes, erythrocytes, hemoglobin, and platelets were related to changes in air pollutant concentration. Daily NO2 levels exhibited significant differences between baseline years and the 2010 Asian Game period. We observed significant reductions in leukocyte and neutrophils counts levels, by 15.51% and 23.01%, from pre-Asian Games to during-Asian Games, respectively. In the post-Asian Game period, most pollutants approximated pre-Asian Game period levels, and similar effects were demonstrated in leukocyte and neutrophil counts. For both items, we identified significant increases resulting from elevated NO2 at lag days 0-2/5-6. We concluded that reductions in pollutants during the intervention period were associated with inactivation of hematological events in COPD.

PMID: 29409586 [PubMed - in process]

The FREGAT biobank: a clinico-biological database dedicated to esophageal and gastric cancers.

Thu, 02/08/2018 - 12:53

The FREGAT biobank: a clinico-biological database dedicated to esophageal and gastric cancers.

BMC Cancer. 2018 Feb 06;18(1):139

Authors: Mariette C, Renaud F, Piessen G, Gele P, Copin MC, Leteurtre E, Delaeter C, Dib M, Clisant S, Harter V, Bonnetain F, Duhamel A, Christophe V, Adenis A, Fregat Working Group

Abstract
BACKGROUND: While the incidence of esophageal and gastric cancers is increasing, the prognosis of these cancers remains bleak. Endoscopy and surgery are the standard treatments for localized tumors, but multimodal treatments, associated chemotherapy, targeted therapies, immunotherapy, radiotherapy, and surgery are needed for the vast majority of patients who present with locally advanced or metastatic disease at diagnosis. Although survival has improved, most patients still present with advanced disease at diagnosis. In addition, most patients exhibit a poor or incomplete response to treatment, experience early recurrence and have an impaired quality of life. Compared with several other cancers, the therapeutic approach is not personalized, and research is much less developed. It is, therefore, urgent to hasten the development of research protocols, and consequently, develop a large, ambitious and innovative tool through which future scientific questions may be answered. This research must be patient-related so that rapid feedback to the bedside is achieved and should aim to identify clinical-, biological- and tumor-related factors that are associated with treatment resistance. Finally, this research should also seek to explain epidemiological and social facets of disease behavior.
METHODS: The prospective FREGAT database, established by the French National Cancer Institute, is focused on adult patients with carcinomas of the esophagus and stomach and on whatever might be the tumor stage or therapeutic strategy. The database includes epidemiological, clinical, and tumor characteristics data as well as follow-up, human and social sciences quality of life data, along with a tumor and serum bank.
DISCUSSION: This innovative method of research will allow for the banking of millions of data for the development of excellent basic, translational and clinical research programs for esophageal and gastric cancer. This will ultimately improve general knowledge of these diseases, therapeutic strategies and patient survival. This database was initially developed in France on a nationwide basis, but currently, the database is available for worldwide contributions with respect to the input of patient data or the request for data for scientific projects.
TRIAL REGISTRATION: The FREGAT database has a dedicated website ( www.fregat-database.org ) and is registered on the Clinicaltrials.gov site, number NCT 02526095 , since August 8, 2015.

PMID: 29409462 [PubMed - in process]

Genetic association of telomere length with hepatocellular carcinoma risk: A Mendelian randomization analysis.

Thu, 02/08/2018 - 12:53
Related Articles

Genetic association of telomere length with hepatocellular carcinoma risk: A Mendelian randomization analysis.

Cancer Epidemiol. 2017 10;50(Pt A):39-45

Authors: Cheng Y, Yu C, Huang M, Du F, Song C, Ma Z, Zhai X, Yang Y, Liu J, Bei JX, Jia W, Jin G, Li S, Zhou W, Liu J, Dai J, Hu Z

Abstract
BACKGROUND: Observational studies show an association between telomere length and Hepatocellular carcinoma (HCC) risk, but the relationship is controversial. Particularly, it remains unclear whether the association is due to confounding or biases inherent in conventional epidemiological studies. Here, we applied Mendelian randomization approach to evaluate whether telomere length is causally associated with HCC risk.
METHODS: Individual-level data were from HBV-related HCC Genome-wide association studies (1,538 HBV positive HCC patients and 1,465 HBV positive controls). Genetic risk score, as proxy for actual measured telomere length, derived from nine telomere length-associated genetic variants was used to evaluate the effect of telomere length on HCC risk.
RESULTS: We observed a significant risk signal between genetically increased telomere length and HBV-related HCC risk (OR=2.09, 95% CI 1.32-3.31, P=0.002). Furthermore, a U-shaped curve was fitted by the restricted cubic spline curve, which indicated that either short or long telomere length would increase HCC risk (P=0.0022 for non-linearity test). Subgroup analysis did not reveal significant heterogeneity between different age, gender, smoking status and drinking status groups.
CONCLUSIONS: Our results indicated that a genetic background that favors longer or shorter telomere length may increase HBV-related HCC risk-a U-shaped association.

PMID: 28797893 [PubMed - indexed for MEDLINE]

Behavioural characterization of AnkyrinG deficient mice, a model for ANK3 related disorders.

Thu, 02/08/2018 - 12:53
Related Articles

Behavioural characterization of AnkyrinG deficient mice, a model for ANK3 related disorders.

Behav Brain Res. 2017 Jun 15;328:218-226

Authors: van der Werf IM, Van Dam D, Missault S, Yalcin B, De Deyn PP, Vandeweyer G, Kooy RF

Abstract
ANK3 encodes AnkyrinG (AnkG), a member of the Ankyrin family that is expressed in several different isoforms in many tissues. A unique serine-rich domain and tail domain in the two largest isoforms of AnkG (270 and 480kDa), restrict AnkG to the axon initial segment and nodes of Ranvier of myelinated neurons. At these sites, AnkG is a master regulator, coordinating the strict clustering of components necessary for proper action potential initiation and propagation along the axon. These components include voltage-gated sodium channels, potassium channels and members of the L1 cell adhesion molecule family. Genetic variation in the ANK3 gene has been linked to a range of neuropsychiatric and neurodevelopmental disorders in human, including schizophrenia, bipolar disorder, intellectual disability and autism spectrum disorders. Here, we study the effect of reduced expression of the large isoforms of Ank3 on cognition and behaviour using a heterozygous knockout mouse model. In three independent behavioural tests, being the open field test, elevated plus maze and social interaction test, we found evidence for increased anxiety in our Ank3 mouse model. Besides, we observed specific neuroanatomical defects in heterozygous knockout mice, including a smaller cingulate cortex, granular retrosplenial cortex, primary motor cortex and fimbria of the hippocampus.

PMID: 28411148 [PubMed - indexed for MEDLINE]

Increased levels of cell-free mitochondrial DNA in the cerebrospinal fluid of patients with multiple sclerosis.

Thu, 02/08/2018 - 12:53
Related Articles

Increased levels of cell-free mitochondrial DNA in the cerebrospinal fluid of patients with multiple sclerosis.

Mitochondrion. 2017 May;34:32-35

Authors: Varhaug KN, Vedeler CA, Myhr KM, Aarseth JH, Tzoulis C, Bindoff LA

Abstract
Mitochondrial DNA (mtDNA) can act as damage-associated molecular pattern molecule (DAMP) and initiate an inflammatory response. We hypothesized that the concentration of mtDNA might reflect inflammatory activity in multiple sclerosis and investigated therefore levels of cell-free mitochondrial DNA in cerebrospinal fluid of patients with relapsing-remitting multiple sclerosis. Significantly higher levels of mtDNA were found in patients compared to controls and there was an inverse correlation between disease duration and mtDNA concentration. Our study suggests that mitochondria can be involved early in multiple sclerosis, but whether this is as an initiator of the inflammatory response or part of its maintenance is unclear. Further, our study suggests that changes in mtDNA may provide a novel marker for early disease activity.

PMID: 28017684 [PubMed - indexed for MEDLINE]

Dichloroacetate potentiates tamoxifen-induced cell death in breast cancer cells via downregulation of the epidermal growth factor receptor.

Thu, 02/08/2018 - 12:53
Related Articles

Dichloroacetate potentiates tamoxifen-induced cell death in breast cancer cells via downregulation of the epidermal growth factor receptor.

Oncotarget. 2016 Sep 13;7(37):59809-59819

Authors: Woo SH, Seo SK, Park Y, Kim EK, Seong MK, Kim HA, Song JY, Hwang SG, Lee JK, Noh WC, Park IC

Abstract
Metabolic reprogramming in cancer cells has recently been recognized as an essential hallmark of neoplasia. In this context, metabolic alterations represent an attractive therapeutic target, and encouraging results with drugs targeting various metabolic processes have been obtained in preclinical studies. Recently, several studies have suggested that dichloroacetate (DCA), a specific pyruvate dehydrogenase kinase inhibitor, may be a potential anticancer drug in a large number of diverse tumors. However, the precise mechanism is not fully understood, which is important for the use of DCA in cancer treatment. In the present study, we found that DCA sensitized MCF7 breast cancer cells to tamoxifen-induced cell death by decreasing epidermal growth factor receptor (EGFR) expression. The downregulation of EGFR was caused by degradation of the protein. Furthermore, p38 mitogen-activated protein kinase played an important role in DCA/tamoxifen-induced EGFR degradation. Finally, DCA also promoted comparable tamoxifen-induced cell death in tamoxifen-resistant MCF7 cells, which were established by long-term treatment with tamoxifen. In summary, our results suggest that DCA is an attractive potential drug that sensitizes cells to tamoxifen-induced cell death and overcome tamoxifen resistance via downregulation of EGFR expression in breast cancer cells.

PMID: 27494858 [PubMed - indexed for MEDLINE]

Effect of Hot Tea Consumption and Its Interactions With Alcohol and Tobacco Use on the Risk for Esophageal Cancer: A Population-Based Cohort Study.

Wed, 02/07/2018 - 12:32

Effect of Hot Tea Consumption and Its Interactions With Alcohol and Tobacco Use on the Risk for Esophageal Cancer: A Population-Based Cohort Study.

Ann Intern Med. 2018 Feb 06;:

Authors: Yu C, Tang H, Guo Y, Bian Z, Yang L, Chen Y, Tang A, Zhou X, Yang X, Chen J, Chen Z, Lv J, Li L, China Kadoorie Biobank Collaborative Group

Abstract
Background: Although consumption of tea at high-temperatures has been suggested as a risk factor for esophageal cancer, an association has not been observed consistently, and whether any relationship is independent of alcohol and tobacco exposure has not been evaluated.
Objective: To examine whether high-temperature tea drinking, along with the established risk factors of alcohol consumption and smoking, is associated with esophageal cancer risk.
Design: China Kadoorie Biobank, a prospective cohort study established during 2004 to 2008.
Setting: 10 areas across China.
Participants: 456 155 persons aged 30 to 79 years. Those who had cancer at baseline or who reduced consumption of tea, alcohol, or tobacco before baseline were excluded.
Measurements: The usual temperature at which tea was consumed, other tea consumption metrics, and lifestyle behaviors were self-reported once, at baseline. Outcome was esophageal cancer incidence up to 2015.
Results: During a median follow-up of 9.2 years, 1731 incident esophageal cancer cases were documented. High-temperature tea drinking combined with either alcohol consumption or smoking was associated with a greater risk for esophageal cancer than hot tea drinking alone. Compared with participants who drank tea less than weekly and consumed fewer than 15 g of alcohol daily, those who drank burning-hot tea and 15 g or more of alcohol daily had the greatest risk for esophageal cancer (hazard ratio [HR], 5.00 [95% CI, 3.64 to 6.88]). Likewise, the HR for current smokers who drank burning-hot tea daily was 2.03 (CI, 1.55 to 2.67).
Limitation: Tea consumption was self-reported once, at baseline, leading to potential nondifferential misclassification and attenuation of the association.
Conclusion: Drinking tea at high temperatures is associated with an increased risk for esophageal cancer when combined with excessive alcohol or tobacco use.
Primary Funding Source: National Natural Science Foundation of China and National Key Research and Development Program.

PMID: 29404576 [PubMed - as supplied by publisher]