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Showing 100 Latest Publications
TitleDate Created
Exploratory Biomarker Study of the Triple Reuptake Inhibitor SEP-432 Compared to the Dual Reuptake Inhibitor Duloxetine in Healthy Normal Subjects.Friday, February 05, 2016
Sramek JJ, Hardy LW, Bieck P, Zamora C, Versavel M, Kharidia J, Grinnell T, Chen YL, Sullivan M, Ding H, Cutler NR,
CNS neuroscience & therapeutics. 5-Feb-2016
CSF monoamine biomarkers confirmed central NET activity for SEP-432 and duloxetine's dual reuptake inhibition.
Identification of β-glucosidase 1 as a biomarker and its high expression in hepatocellular carcinoma is associated with resistance to chemotherapy drugs.Friday, February 05, 2016
Zhang Y, Zhu K, Miao X, Hu X, Wang T,
Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals. 5-Feb-2016
Our data support β-glucosidase 1 as a HCC biomarker due to its prognosis significance.
Laboratory Information Systems in Molecular Diagnostics: Why Molecular Diagnostics Data are Different.Saturday, February 06, 2016
Lee RE, Henricks WH, Sirintrapun SJ,
Advances in anatomic pathology. Mar-2016
Molecular diagnostic testing presents new challenges to information management that are yet to be sufficiently addressed by currently available information systems for the molecular laboratory. These challenges relate to unique aspects of molecular genetic testing: molecular test ordering, informed consent issues, diverse specimen types that encompass the full breadth of specimens handled by traditional anatomic and clinical pathology information systems, data structures and data elements specific to molecular testing, varied testing workflows and protocols, diverse instrument outputs, unique needs and requirements of molecular test reporting, and nuances related to the dissemination of molecular pathology test reports. By satisfactorily addressing these needs in molecular test data management, a laboratory information system designed for the unique needs of molecular diagnostics presents a compelling reason to migrate away from the current paper and spreadsheet information management that many molecular laboratories currently use. This paper reviews the issues and challenges of information management in the molecular diagnostics laboratory.
Solitary Fibrous Tumor/Hemangiopericytoma Dichotomy Revisited: A Restless Family of Neoplasms in the CNS.Saturday, February 06, 2016
Yalcin CE, Tihan T,
Advances in anatomic pathology. Mar-2016
Solitary fibrous tumor (SFT) and hemangiopericytoma (HPC) both entered the literature as separate entities in the early to mid 1900s. In contrast to their central nervous system (CNS) counterparts, there has been a tendency to consider these 2 entities as 1 since the early 1990s, as soft tissue SFT gradually included the tumors previously diagnosed as HPC. The most recent World Health Organization (WHO) classification of the tumors of soft tissue considered the term HPC obsolete, and places all such tumors within the extrapleural SFT category. In contrast, CNS SFT and HPC continue to be regarded as different entities in the latest version of the WHO CNS tumor classification. A change in this approach is currently being considered for the upcoming revision of the WHO scheme, but it is not quite clear whether such a change will be as drastic as the one adopted by the soft tissue and bone tumor working group. This article focuses on the historical evolution of these 2 labels as primary CNS neoplasms, and reviews their differences and similarities in terms of clinical, pathologic, and molecular features.
The State of the Art in Colorectal Cancer Molecular Biomarker Testing.Saturday, February 06, 2016
Pillai RK, Lopategui JR, Dhall D, Guindi M, Slavin T, Lofton-Day CE, Patterson SD,
Advances in anatomic pathology. Mar-2016
The number of molecular biomarkers to inform treatment decisions in patients with metastatic colorectal cancer (mCRC) continues to expand and with it the methodologies that can be employed to evaluate these biomarkers. Beyond standard diagnostic and prognostic biomarkers, such as those used for Lynch syndrome, mutations in KRAS exon 2 are well established as predictive for lack of response to the antiepidermal growth factor receptor therapies panitumumab and cetuximab. Recent studies have extended these findings by demonstrating that mutations in KRAS exons 3 and 4 and in NRAS exons 2, 3, and 4 (with all KRAS and NRAS mutations collectively referred to as RAS) are also predictive for treatment outcomes among patients with mCRC receiving panitumumab and cetuximab in combination with chemotherapy or as monotherapy. Consequently, evaluation of these additional loci has been incorporated into current clinical guidelines, and pathologists will need to develop testing procedures and algorithms to reliably and rapidly evaluate RAS status. With the increased number of mutations that must be examined to evaluate the status of RAS and other emerging biomarkers, next-generation sequencing technologies are likely to become increasingly important in mCRC testing. This review describes new considerations for pathologists that have arisen as a consequence of the incorporation of additional biomarker testing into clinical practice for mCRC.
Laryngeal Squamous Intraepithelial Lesions: An Updated Review on Etiology, Classification, Molecular Changes, and Treatment.Saturday, February 06, 2016
Gale N, Gnepp DR, Poljak M, Strojan P, Cardesa A, Helliwell T, Šifrer R, Volavšek M, Sandison A, Zidar N,
Advances in anatomic pathology. Mar-2016
Laryngeal carcinogenesis is a multistep process, characterized by an accumulation of genetic changes associated with architectural and cytologic alterations, ranging from squamous hyperplasia to carcinoma in situ and encompassed by the terminology of squamous intraepithelial lesions (SILs). The etiology, classification, genetic changes, and malignant progression of these lesions are reviewed. Tobacco remains the principal etiological factor with gastroesophageal reflux disease recently considered as a possible factor. In contrast, there is little evidence that microbiological agents, especially human papillomavirus infection, are frequently involved in laryngeal carcinogenesis and probably <10% of SILs are driven by biologically active human papillomavirus infection. Light microscopy, despite a degree of subjectivity, remains the mainstay of accurate diagnosis, prognosis, and guidance for a patient's treatment. The currently used classifications, the dysplasia system, squamous intraepithelial neoplasia, and the Ljubljana classification, reflect different standpoints on this important topic. The modified Ljubljana classification, with good interobserver agreement, could be considered as a proposal for a unified classification of laryngeal SILs. This review also briefly discusses recently discovered genetic changes, such as CDKN2A and CTNNB1 genes, and chromosome instability of chromosomes 1 and 7; however, none of these can at present improve histologic diagnosis. Malignant progression of precursor lesions varies from 2% to 74%, according to different studies. Cold-steel microinstruments, CO2 laser, and radiotherapy are used to treat the different grades of precursor lesions. There is as yet no worldwide agreement on the treatment of high-grade lesions and carcinoma in situ.
(99m)Tc-DPD uptake reflects amyloid fibril composition in hereditary transthyretin amyloidosis.Friday, February 05, 2016
Pilebro B, Suhr OB, Näslund U, Westermark P, Lindqvist P, Sundström T,
Upsala journal of medical sciences. 5-Feb-2016
Aims In transthyretin amyloid (ATTR) amyloidosis various principal phenotypes have been described: cardiac, neuropathic, or a mixed cardiac and neuropathic. In addition, two different types of amyloid fibrils have been identified (type A and type B). Type B fibrils have thus far only been found in predominantly early-onset V30M and in patients carrying the Y114C mutation, whereas type A is noted in all other mutations currently examined as well as in wild-type ATTR amyloidosis. The fibril type is a determinant of the ATTR V30M disease phenotype. (99m)Tc-DPD scintigraphy is a highly sensitive method for diagnosing heart involvement in ATTR amyloidosis. The objective of this study was to determine the relationship between ATTR fibril composition and (99m)Tc-DPD scintigraphy outcome in patients with biopsy-proven ATTR amyloidosis. Methods Altogether 55 patients with biopsy-proven diagnosis of ATTR amyloidosis and amyloid fibril composition determined were examined by (99m)Tc-DPD scintigraphy. The patients were grouped and compared according to their type of amyloid fibrils. Cardiovascular evaluation included ECG, echocardiography, and cardiac biomarkers. The medical records were scrutinized to identify subjects with hypertension or other diseases that have an impact on cardiac dimensions. Results A total of 97% with type A and none of the patients with type B fibrils displayed (99m)Tc-DPD uptake at scintigraphy (p < 0.001). Findings from analyses of cardiac biomarkers, ECG, and echocardiography, though significantly different, could not differentiate between type A and B fibrils in individual patients. Conclusion In ATTR amyloidosis, the outcome of (99m)Tc-DPD scintigraphy is strongly related to the patients' transthyretin amyloid fibril composition.
Duration of therapy of ventilator-associated pneumonia.Friday, February 05, 2016
Dimopoulos G, Matthaiou DK,
Current opinion in infectious diseases. 4-Feb-2016
The shortening of the duration of treatment for VAP is promising, as long as a holistic approach that combines methods ensuring the adequate sterilization of septic foci, the optimization of antibiotic levels, the multifaceted delivery of antimicrobials in the lung and the usage of biomarkers that allow the monitoring of the disease course and the effectiveness of administered treatment are incorporated in clinical practice.
Molecular evolution of troponin I and a role of its N-terminal extension in nematode locomotion.Friday, February 05, 2016
Barnes DE, Hwang H, Ono K, Lu H, Ono S,
Cytoskeleton (Hoboken, N.J.). 5-Feb-2016
The troponin complex, composed of troponin T (TnT), troponin I (TnI), and troponin C (TnC), is the major calcium-dependent regulator of muscle contraction, which is present widely in both vertebrates and invertebrates. Little is known about evolutionary aspects of troponin in the animal kingdom. Using a combination of data mining and functional analysis of TnI, we report evidence that an N-terminal extension of TnI is present in most of bilaterian animals as a functionally important domain. Troponin components have been reported in species in most of representative bilaterian phyla. Comparison of TnI sequences shows that the core domains are conserved in all examined TnIs, and that N- and C-terminal extensions are variable among isoforms and species. In particular, N-terminal extensions are present in all protostome TnIs and chordate cardiac TnIs but lost in a subset of chordate TnIs including vertebrate skeletal-muscle isoforms. Transgenic rescue experiments in C. elegans striated muscle show that the N-terminal extension of TnI (UNC-27) is required for coordinated worm locomotion but not in sarcomere assembly and single muscle-contractility kinetics. These results suggest that N-terminal extensions of TnIs are retained from a TnI ancestor as a functional domain. This article is protected by copyright. All rights reserved.
O-020 PMN CD64: Therapeutic Target for Sustained Remission During Infliximab Maintenance.Friday, February 05, 2016
Minar P, Jackson K, Tsai YT, Denson L,
Inflammatory bowel diseases. Mar-2016
Although anti-TNF therapies are currently the most effective medical treatment for CD, fewer than 60% will remain on the same anti-TNF after 3 years. We have shown that the PMN CD64 index is a reliable surrogate marker of ongoing intestinal inflammation in patients receiving infliximab and a larger validation cohort would support its use as the treat-to-target biomarker in CD.
O-016 YI Longitudinal Study of Circulating miRNA Biomarkers in Inflammatory Bowel Disease.Friday, February 05, 2016
Viennois E, Zhao Y, Zhang M, Han M, Merlin D,
Inflammatory bowel diseases. Mar-2016
We used a mouse model to establish a putative miRNA signature of colitis, and determined that it could be a useful tool for following the evolution of intestinal inflammation in mice. Future work is warranted to adapt this concept to human serum samples and identify IBD specific miRNA patterns in human patients.
Thrombosis-associated antifibrinogen IgG1 κ impairs fibrin polymerization and enhances platelet activation.Friday, February 05, 2016
Galanakis DK, Spitzer ED, Perrotta P, Nagaswami C, Marchi R, Spitzer S, Refailovich M, Smith RE, Zhang L, Marmorat C, Weisel JW,
Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis. 4-Feb-2016
The present study extends our previous investigation of circulating antibody/fibrinogen/C1q complexes (FgIgC) associated with thrombosis in a heterophenotypic AαR16C proband, by focusing on the molecular and functional characteristics of the FgIgC, isolated by cryoprecipitation, FgIgC components were demonstrated by SDS-PAGE and by rotary shadowing electron microscopy. Affinity chromatography was used to isolate IgG and fibrinogen from FgIgC. Thrombin-induced clots were examined by scanning electron microscopy and turbidity measurements. IgG/fibrinogen binding was measured by ELISA. Fibrinogen Aα1-19 peptides, cleaved by thrombin from fragment N-DSK, were examined by mass spectrometry. Clot stiffness, platelet release of P-selectin, and fibrinogen self-assembly were assessed by thromboelastography, flow cytometry, and atomic force microscopy, respectively. The FgIgC effects included the following: increased P-selectin release from gel-sieved platelets, finer fiber networks and decreased stiffness of its clots, and marked inhibition of fibrinogen self-assembly. The abnormal proband fibrinogen structure displayed phosphorylated AαR16C-AαR16C homodimers and AαR16C-glutathione heterodimers. ELISA measurements disclosed pronounced binding by proband fibrinogen to proband IgG, which was blocked by the IgG's Fab fragment and by proband, but not by normal plasmic fragment E1. There was appreciable, but much weaker, binding to normal fibrinogen, to its fragments E1, and D1, and to homodimeric AαR16C fibrinogen. The antibody's primary target epitope included heterodimeric AαR16C-glutathione; a secondary epitope resided in the D region. Moreover, both the enhanced platelet activation (i.e. increased P-selectin release induced by FgIgC) and the highly phosphorylated FpA (i.e. resulting in its accelerated release by thrombin) may have contributed to the thrombotic diathesis.
Application of SELDI-TOF in N-glycopeptides Profiling of the Urine from Patients with Endometrial, Ovarian and Cervical Cancer.Friday, February 05, 2016
Mu AK, Lim BK, Aminudin N, Hashim OH, Shuib AS,
Archives of physiology and biochemistry. 5-Feb-2016
The findings of this study suggest urinary glycopeptides m/z 1201 and 1449 may serve as potential biomarkers for the early detection of ECa, OCa and CCa although this requires further extensive validation on clinically representative populations.
Whole Transcriptome Analysis of Hypertension Induced Cardiac Injury Using Deep Sequencing.Friday, February 05, 2016
Li TT, Li XY, Jia LX, Zhang J, Zhang WM, Li YL, Qi YF, Du J,
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology. 8-Feb-2016
Our study provides a comprehensive understanding of the transcriptome events in hypertension-induced cardiac pathology.
Recent developments in severe sepsis research: from bench to bedside and back.Friday, February 05, 2016
Rasid O, Cavaillon JM,
Future microbiology. 5-Feb-2016
Severe sepsis remains a worldwide threat, not only in industrialized countries, due to their aging population, but also in developing countries where there still are numerous cases of neonatal and puerperal sepsis. Tools for early diagnosis, a prerequisite for rapid and appropriate antibiotic therapy, are still required. In this review, we highlight some recent developments in our understanding of the associated systemic inflammatory response that help deciphering pathophysiology (e.g., epigenetic, miRNA, regulatory loops, compartmentalization, apoptosis and synergy) and discuss some of the consequences of sepsis (e.g., immune status, neurological and muscular alterations). We also emphasize the challenge to better define animal models and discuss past failures in clinical investigations in order to define new efficient therapies.
Association of Urinary Neutrophil Gelatinase-Associated Lipocalin with Long-Term Renal Outcomes in Icu Survivors: a Retrospective Observational Cohort Study.Friday, February 05, 2016
Isshiki R, Asada T, Sato D, Sumida M, Hamasaki Y, Inokuchi R, Matsubara T, Ishii T, Yahagi N, Nangaku M, Noiri E, Doi K,
Shock (Augusta, Ga.). 3-Feb-2016
Urinary NGAL measured at ICU admission was significantly associated with long-term renal outcomes after hospital discharge in MAKE-free ICU survivors. Urinary NGAL measurements at ICU might be useful to identify a high risk population of kidney disease progression after intensive care.
Biomarkers or Clinical Observations to Identify (outcome of) Emergency Department Patients with Infection?Friday, February 05, 2016
Quinten V, Ter Maaten JC, Ligtenberg JJ, van Meurs M,
Shock (Augusta, Ga.). 3-Feb-2016
Screening of PAX6 gene in Italian congenital aniridia patients revealed four novel mutations.Friday, February 05, 2016
Primignani P, Allegrini D, Manfredini E, Romitti L, Mauri L, Patrosso MC, Veniani E, Franzoni A, Longo AD, Gesu GP, Piozzi E, Damante G, Penco S,
Ophthalmic genetics. 5-Feb-2016
It is important to establish the molecular diagnosis early to avoid repeated and long-term screening for Wilms tumor. Our work further emphasizes that a wide range of ocular phenotypes are associated with loss of function PAX6 mutations. In addition to the possibility of stochastic variations, other genetic variations could play a role as modifier genes, thus giving rise to the observed different ocular phenotypes.
Monitoring Tyrosinase Expression in Non-metastatic and Metastatic Melanoma Tissues by Scanning Electrochemical Microscopy.Friday, February 05, 2016
Lin TE, Bondarenko A, Lesch A, Pick H, Cortés-Salazar F, Girault HH,
Angewandte Chemie (International ed. in English). 5-Feb-2016
Although tremendous progress has been made in the diagnosis of melanoma, the identification of different stages of malignancy in a reliable way remains challenging. Current strategies rely on optical monitoring of the concentration and spatial distribution of specific biomarkers. State-of-the-art optical methods can be affected by background-color interference and autofluorescence. We overcame these shortcomings by employing scanning electrochemical microscopy (SECM) to map the prognostic indicator tyrosinase (TyR) in non-metastatic and metastatic melanoma tissues by using soft-stylus microelectrodes. Electrochemical readout of the TyR distribution was enabled by adapting an immunochemical method. SECM can overcome the limitations of optical methods and opens unprecedented possibilities for improved diagnosis and understanding of the spatial distribution of TyR in different melanoma stages.
Biomarkers of Exposure to Polycyclic Aromatic Hydrocarbons and Cognitive Function among Elderly in the United States (National Health and Nutrition Examination Survey: 2001-2002).Friday, February 05, 2016
Best EA, Juarez-Colunga E, James K, LeBlanc WG, Serdar B,
PloS one. 5-2-2016
Recent studies report a link between common environmental exposures, such as particulate matter air pollution and tobacco smoke, and decline in cognitive function. The purpose of this study was to assess the association between exposure to polycyclic aromatic hydrocarbons (PAHs), a selected group of chemicals present in particulate matter and tobacco smoke, and measures of cognitive performance among elderly in the general population. This cross-sectional analysis involved data from 454 individuals aged 60 years and older from the 2001-2002 National Health and Nutrition Examination Survey. The association between PAH exposures (as measured by urinary biomarkers) and cognitive function (digit symbol substitution test (DSST)) was assessed using multiple linear regression analyses. After adjusting for age, socio-economic status and diabetes we observed a negative association between urinary 1-hydroxypyrene, the gold standard of PAH exposure biomarkers, and DSST score. A one percent increase in urinary 1-hydroxypyrene resulted in approximately a 1.8 percent poorer performance on the digit symbol substitution test. Our findings are consistent with previous publications and further suggest that PAHs, at least in part may be responsible for the adverse cognitive effects linked to tobacco smoke and particulate matter air pollution.
Ultrasensitive electrochemical detection of nucleic acid by coupling an autonomous cascade target replication and enzyme/gold nanoparticle-based post-amplification.Friday, February 05, 2016
Liu S, Wei W, Wang Y, Fang L, Wang L, Li F,
Biosensors & bioelectronics. 28-Jan-2016
Owing to the intrinsic importance of nucleic acid as bio-targets, the development of isothermal and ultrasensitive electrochemical DNA biosensor is very essential for biological studies and medical diagnostics. Herein, the autonomous cascade DNA replication strategy was effectively married with the enzyme/gold nanoparticle-based post-amplification strategy to promote the detection performance toward target DNA. A hairpin DNA probe (HP) is designed that consists of an overhang at 3'-end as the recognition unit for target DNA, a recognition site for nicking endonuclease, and an alkane spacer to terminate polymerization reaction. The autonomous DNA replication-scission-displacement reaction operated by the nicking endonuclease/KF polymerase induced the autocatalytic opening of HP, which was then specifically bound by the enzyme/gold nanoparticles for further dual-signal amplification toward target-related sensing events. A low detection limit of 0.065fM with an excellent selectivity toward target DNA could be achieved. The proposed biosensor could be also easily regenerated for target detection. The developed biosensor creates an opportunity for the effective coupling of the target replication with post-amplification strategies and thus opens a promising avenue for the detection of nucleic acid with low abundance in bioanalysis and clinical biomedicine.
CDX2: Linking Cell and Patient Fates in Colon Cancer.Saturday, February 06, 2016
Fearon ER, Huang EH,
Cell stem cell. 4-Feb-2016
Administering adjuvant chemotherapy to stage II colon cancer patients is controversial due to limited benefit observed for this subpopulation. Recently, Dalerba et al. (2016) identified a subgroup of stage II patients that might benefit from adjuvant chemotherapy based on lack of CDX2 expression in their cancer stem cells.
Exercise-induced oxidatively damaged DNA in humans: evaluation in plasma or urine?Friday, February 05, 2016
Karpouzi C, Nikolaidis S, Kabasakalis A, Tsalis G, Mougios V,
Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals. 5-Feb-2016
Physical exercise can induce oxidative damage in humans. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) is a widely known biomarker of DNA oxidation, which can be determined in blood and urine. The aim of the present study was to compare these two biological fluids in terms of which is more suitable for the estimation of the oxidative damage of DNA by measuring the concentration of 8-OHdG one hour after maximal exercise by enzyme immunoassay. The concentration of 8-OHdG increased with exercise only in plasma (p < 0.001), and values differed between exercise tests in both plasma and urine (p < 0.05). In conclusion, plasma appears to be more sensitive to exercise-induced 8-OHdG changes than urine and, hence, a more appropriate medium for assessing oxidative damage of DNA, although the poor repeatability of the measurement needs to be addressed in future studies.
Reply to specific gene patterns and molecular pathways related to human carcinogenesis in different populations among various geographic locations.Friday, February 05, 2016
Siraj AK, Beg S, Al-Kuraya KS,
Cancer. 5-Feb-2016
Heparanase promotes myeloma progression by inducing mesenchymal features and motility of myeloma cells.Friday, February 05, 2016
Li J, Pan Q, Rowan PD, Trotter TN, Peker D, Regal KM, Javed A, Suva LJ, Yang Y,
Oncotarget. 3-Feb-2016
Bone dissemination and bone disease occur in approximately 80% of patients with multiple myeloma (MM) and are a major cause of patient mortality. We previously demonstrated that MM cell-derived heparanase (HPSE) is a major driver of MM dissemination to and progression in new bone sites. However the mechanism(s) by which HPSE promotes MM progression remains unclear. In the present study, we investigated the involvement of mesenchymal features in HPSE-promoted MM progression in bone. Using a combination of molecular, biochemical, cellular, and in vivo approaches, we demonstrated that (1) HPSE enhanced the expression of mesenchymal markers in both MM and vascular endothelial cells; (2) HPSE expression in patient myeloma cells positively correlated with the expression of the mesenchymal markers vimentin and fibronectin. Additional mechanistic studies revealed that the enhanced mesenchymal-like phenotype induced by HPSE in MM cells is due, at least in part, to the stimulation of the ERK signaling pathway. Finally, knockdown of vimentin in HPSE expressing MM cells resulted in significantly attenuated MM cell dissemination and tumor growth in vivo. Collectively, these data demonstrate that the mesenchymal features induced by HPSE in MM cells contribute to enhanced tumor cell motility and bone-dissemination.
Do biomarkers of exposure and effect correlate with internal exposure to PAHs in swine?Friday, February 05, 2016
Peters RE, Wickstrom M, Siciliano SD,
Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals. 5-Feb-2016
Humans are commonly exposed to polycyclic aromatic hydrocarbons (PAHs), a family of compounds present as mixtures in the environment. This study exposed swine to PAH mixtures in single and subacute dose regimens and collected liver and ileum tissue to measure cytochrome P450 mRNA expression and enzyme activity as biomarkers of exposure and DNA adducts and oxidized proteins as biomarkers of effect. Micronucleated reticulocytes were measured as systemic biomarkers of effect. Duration of exposure did not influence biomarkers of exposure, though exposure duration produced significant increases in DNA adducts and oxidative stress. Micronucleated reticulocyte numbers were not affected by exposure length.
Evaluation of the antineoplastic activity of gallic acid in oral squamous cell carcinoma under hypoxic conditions.Friday, February 05, 2016
Guimarães TA, Farias LC, de Carvalho Fraga CA, Feltenberger JD, Melo GA, Coletta RD, Souza Santos SH, de Paula AM, Sena Guimarães AL,
Anti-cancer drugs. 4-Feb-2016
The purpose of the current study was to develop and test a theoretical model that could explain the mechanism of action of gallic acid (GA) in the oral squamous cell carcinoma context for the first time. The theoretical model was developed using bioinformatics and interaction network analysis to evaluate the effect of GA on oral squamous cell carcinoma. In a second step to confirm theoretical results, migration, invasion, proliferation, and gene expression (Col1A1, E-cadherin, HIF-1α, and caspase-3) were performed under normoxic and hypoxic conditions. Our study indicated that treatment with GA resulted in the inhibition of cell proliferation, migration, and invasion in neoplastic cells. Observation of the molecular mechanism showed that GA upregulates E-cadherin expression and downregulates Col1A1 and HIF-1α expression, suggesting that GA might be a potential anticancer compound. In conclusion, the present study demonstrated that GA significantly reduces cell proliferation, invasion, and migration by increasing E-cadherin and repressing Col1A1.
Current laboratory approaches to diagnosis of CNS fungal infections.Friday, February 05, 2016
Lyons JL, Zhang SX,
Future microbiology. 5-Feb-2016
Fibroblast growth factor family aberrations as a putative driver of head and neck squamous cell carcinoma in an epidemiologically low-risk patient as defined by targeted sequencing.Friday, February 05, 2016
Tillman BN, Yanik M, Birkeland AC, Liu CJ, Hovelson DH, Cani AK, Palanisamy N, Carskadon S, Carey TE, Bradford CR, Tomlins SA, McHugh JB, Spector ME, Chad Brenner J,
Head & neck. 5-Feb-2016
Together, these data suggest that FGF signaling may be critical for a subset of patients with HNSCC independent of other known pathways and provides rationale for leveraging patients with ELR-HNSCC to define molecular subsets of high-risk HNSCC. © 2016 Wiley Periodicals, Inc. Head Neck, 2016.
Reliability of urine lactate as a novel biomarker of lactate production capacity in maximal swimming.Friday, February 05, 2016
Nikolaidis S, Karpouzi C, Tsalis G, Kabasakalis A, Papaioannou KG, Mougios V,
Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals. 5-Feb-2016
Although promising as a biomarker of lactate production capacity, urine lactate requires further research to improve its reliability.
Biologic and clinical characteristics of adolescent and young adult cancers: Acute lymphoblastic leukemia, colorectal cancer, breast cancer, melanoma, and sarcoma.Friday, February 05, 2016
Tricoli JV, Blair DG, Anders CK, Bleyer A, Boardman LA, Khan J, Kummar S, Hayes-Lattin B, Hunger SP, Merchant M, Seibel NL, Thurin M, Willman CL,
Cancer. 5-Feb-2016
Adolescent and young adult (AYA) patients with cancer have not attained the same improvements in overall survival as either younger children or older adults. One possible reason for this disparity may be that the AYA cancers exhibit unique biologic characteristics, resulting in differences in clinical and treatment resistance behaviors. This report from the biologic component of the jointly sponsored National Cancer Institute and LiveStrong Foundation workshop entitled "Next Steps in Adolescent and Young Adult Oncology" summarizes the current status of biologic and translational research progress for 5 AYA cancers; colorectal cancer breast cancer, acute lymphoblastic leukemia, melanoma, and sarcoma. Conclusions from this meeting included the need for basic biologic, genomic, and model development for AYA cancers as well as translational research studies to elucidate any fundamental differences between pediatric, AYA, and adult cancers. The biologic questions for future research are whether there are mutational or signaling pathway differences (for example, between adult and AYA colorectal cancer) that can be clinically exploited to develop novel therapies for treating AYA cancers and to develop companion diagnostics. Cancer 2016. © 2016 American Cancer Society.
Potential Role of Oestrogen Modulation in the Treatment of Neurocognitive Deficits in Schizophrenia.Friday, February 05, 2016
Weickert TW, Allen KM, Weickert CS,
CNS drugs. 5-Feb-2016
Cognitive deficits are prevalent in schizophrenia, and these deficits represent a disabling aspect of the illness for which there are no current effective treatments. Recent work has shown that sex hormone levels correlate with brain activity and cognitive abilities differentially in patients with schizophrenia relative to healthy control groups. There is emerging evidence suggesting that oestrogen-based therapies may be useful in reversing the cognitive deficits associated with schizophrenia. To date, the results from clinical trials using oestrogen-based therapies to reverse cognitive impairment in schizophrenia have shown that the selective oestrogen receptor modulator raloxifene may be useful to improve attention, memory, learning and the associated brain activity in chronically ill men and women with schizophrenia or schizoaffective disorder. While these findings of cognitive enhancement with a selective oestrogen receptor modulator in people with schizophrenia are encouraging, additional studies will be required to replicate the initial results, assess the time frame of treatment effects, identify biomarkers in subsets of patients who may be more likely to optimally respond to treatment, and identify a more precise mechanism of action, which may include anti-inflammatory effects of oestrogen-based treatments.
Lactobacillus casei Exerts Anti-Proliferative Effects Accompanied by Apoptotic Cell Death and Up-Regulation of TRAIL in Colon Carcinoma Cells.Friday, February 05, 2016
Tiptiri-Kourpeti A, Spyridopoulou K, Santarmaki V, Aindelis G, Tompoulidou E, Lamprianidou EE, Saxami G, Ypsilantis P, Lampri ES, Simopoulos C, Kotsianidis I, Galanis A, Kourkoutas Y, Dimitrellou D, Chlichlia K,
PloS one. 5-2-2016
Probiotic microorganisms such as lactic acid bacteria (LAB) exert a number of strain-specific health-promoting activities attributed to their immunomodulatory, anti-inflammatory and anti-carcinogenic properties. Despite recent attention, our understanding of the biological processes involved in the beneficial effects of LAB strains is still limited. To this end, the present study investigated the growth-inhibitory effects of Lactobacillus casei ATCC 393 against experimental colon cancer. Administration of live Lactobacillus casei (as well as bacterial components thereof) on murine (CT26) and human (HT29) colon carcinoma cell lines raised a significant concentration- and time-dependent anti-proliferative effect, determined by cell viability assays. Specifically, a dramatic decrease in viability of colon cancer cells co-incubated with 109 CFU/mL L. casei for 24 hours was detected (78% for HT29 and 52% for CT26 cells). In addition, live L. casei induced apoptotic cell death in both cell lines as revealed by annexin V and propidium iodide staining. The significance of the in vitro anti-proliferative effects was further confirmed in an experimental tumor model. Oral daily administration of 109 CFU live L. casei for 13 days significantly inhibited in vivo growth of colon carcinoma cells, resulting in approximately 80% reduction in tumor volume of treated mice. Tumor growth inhibition was accompanied by L. casei-driven up-regulation of the TNF-related apoptosis-inducing ligand TRAIL and down-regulation of Survivin. Taken together, these findings provide evidence for beneficial tumor-inhibitory, anti-proliferative and pro-apoptotic effects driven by this probiotic LAB strain.
The cut-off value for interleukin 34 as an additional potential inflammatory biomarker for the prediction of the risk of diabetic complications.Friday, February 05, 2016
Zorena K, Jachimowicz-Duda O, Wąż P,
Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals. 5-Feb-2016
In the present study, we have decided to evaluate whether serum interleukin 34 (IL-34) levels may have diagnostic value in predicting the risk of vascular diabetic complications. The study included 49 patients with type 2 diabetes mellitus (T2DM) and 23 high-risk group. The receiver operating characteristic (ROC) curve analysis has shown that IL-34 has more discriminatory power than C-reactive protein (CRP) for the risk of diabetic complications. The cut-off value for IL-34 was established as 91.2 pg/mL. The gist of our research was identification of IL-34 as an additional potential inflammatory biomarker for the prediction of the risk of vascular diabetic complications.
Biochip-Based Genotyping Assay for Detection of Polymorphisms in Pigmentation Genes Associated with Cutaneous Melanoma.Friday, February 05, 2016
Fesenko DO, Chudinov AV, Surzhikov SA, Zasedatelev AS,
Genetic testing and molecular biomarkers. 5-Feb-2016
The developed approach proved robust, suggesting that it might be useful for the personalized genotyping of large cohorts of patients.
NOTUM is a potential pharmacodynamic biomarker of Wnt pathway inhibition.Friday, February 05, 2016
Madan B, Ke Z, Lei ZD, Oliver FA, Oshima M, Lee MA, Rozen S, Virshup DM,
Oncotarget. 3-Feb-2016
Activation of Wnt signaling due to Wnt overexpression or mutations of Wnt pathway components is associated with various cancers. Blocking Wnt secretion by inhibiting PORCN enzymatic activity has shown efficacy in a subset of cancers with elevated Wnt signaling. Predicting response to upstream Wnt inhibitors and monitoring response to therapeutics is challenging due to the paucity of well-defined biomarkers. In this study we identify Notum as a potential biomarker for Wnt driven cancers and show that coordinate regulation of NOTUM and AXIN2 expression may be a useful predictor of response to PORCN inhibitors. Most importantly, as NOTUM is a secreted protein and its levels in blood correlate with tumor growth, it has potential as a pharmacodynamic biomarker for PORCN and other Wnt pathway inhibitors.
Mucin glycosylating enzyme GALNT2 suppresses malignancy in gastric adenocarcinoma by reducing MET phosphorylation.Friday, February 05, 2016
Liu SY, Shun CT, Hung KY, Juan HF, Hsu CL, Huang MC, Lai IR,
Oncotarget. 30-Jan-2016
Glycosylation affects malignancy in cancer. Here, we report that N- acetylgalactosaminyltransferase 2 (GALNT2), an enzyme that mediates the initial step of mucin type-O glycosylation, suppresses malignant phenotypes in gastric adenocarcinoma (GCA) by modifying MET (Hepatocyte growth factor receptor) activity. GALNT2 mRNA and protein were downregulated in GCAs, and this reduction was associated with more advanced disease stage and shorter recurrence-free survival. Suppressing GALNT2 expression in GCA cells increased cell growth, migration, and invasion in vitro, and tumor metastasis in vivo. GALNT2 knockdown enhanced phosphorylation of MET and decreased expression of the Tn antigen on MET. Inhibiting MET activity with PHA665752 decreased the malignant phenotypes caused by GALNT2 knockdown in GCA cells. Our results indicate that GALNT2 suppresses the malignant potential of GCA cells and provide novel insights into the significance of O-glycosylation in MET activity and GCA progression.
Selected volatile organic compounds as biomarkers for exposure to tobacco smoke.Friday, February 05, 2016
Jain RB,
Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals. 5-Feb-2016
Cutoff levels on the scales for benzene, ethylbenzene, toluene, styrene, o-xylene and m/p-xylene in blood were developed to classify smokers from non-smokers. Self-reported smoking during the last 5 d was used as the true smoking status. Receiver operating characteristics methods that minimized the difference between specificity and sensitivity were used to develop these cutoffs. Data from National Health and Nutrition Examination Survey for the cycle 2005-2006 were used for this purpose. For the total population, a cutoff of 0.038 ng/ml for benzene was able to classify smokers from non-smokers with a sensitivity of 83.6% and specificity of 83.7%.
Fluorescence In Vivo Hybridization (FIVH) for Detection of Helicobacter pylori Infection in a C57BL/6 Mouse Model.Friday, February 05, 2016
Fontenete S, Leite M, Cappoen D, Santos R, Ginneken CV, Figueiredo C, Wengel J, Cos P, Azevedo NF,
PloS one. 5-2-2016
In the future this methodology can be used in combination with a confocal laser endomicroscope for in vivo diagnosis of H. pylori infection using fluorescent LNA probes, which would be helpful to obtain an immediate diagnosis. Our results proved for the first time that FIVH method is applicable inside the body of a higher-order animal.
Vitamin D Status and Gestational Diabetes: Effect of Smoking Status during Pregnancy.Friday, February 05, 2016
Dodds L, Woolcott CG, Weiler H, Spencer A, Forest JC, Armson BA, Giguère Y,
Paediatric and perinatal epidemiology. 5-Feb-2016
Our study supports the inverse association of vitamin D status with gestational diabetes risk, particularly among women who smoke during pregnancy. More research is needed to confirm this finding and, if confirmed, to determine the mechanism by which the combined effect of smoking and low vitamin D status increases the risk of developing gestational diabetes.
Differential Diagnosis of Intraductal Lesions of the Prostate.Friday, February 05, 2016
Wobker SE, Epstein JI,
The American journal of surgical pathology. 4-Feb-2016
The category of intraductal lesions of the prostate includes a range of primary prostatic and nonprostatic processes with wide variation in prognosis and recommended follow-up. Studies have shown that pathologists are uncomfortable with the diagnosis of these lesions and that the diagnostic reproducibility is low in this category. Despite the diagnostic difficulty, their accurate and reproducible diagnosis is critical for patient management. This review aims to highlight the diagnostic criteria, prognosis, and treatment implications of common intraductal lesions of the prostate. It focuses on the recognition of intraductal carcinoma of the prostate (IDC-P) in prostate needle biopsies and how to distinguish it from its common mimickers, including high-grade prostatic intraepithelial neoplasia, invasive cribriform prostatic adenocarcinoma, urothelial carcinoma extending into prostatic ducts, and prostatic ductal adenocarcinoma. IDC-P is independently associated with higher risk disease, and its identification in a needle biopsy, even in the absence of invasive carcinoma, should compel definitive treatment. Conversely, high-grade prostatic intraepithelial neoplasia has a much better prognosis and in limited quantities does not even warrant a repeat biopsy. IDC-P must be distinguished from urothelial carcinoma involving prostatic ducts, as recommended treatment varies markedly. Ductal adenocarcinoma may confuse the pathologist and clinician by overlapping terminology, and morphology may also mimic IDC-P on occasion. The use of ancillary testing with immunohistochemistry and molecular markers has also been reviewed.
Two Cases of Renal Cell Carcinoma Harboring a Novel STRN-ALK Fusion Gene.Friday, February 05, 2016
Kusano H, Togashi Y, Akiba J, Moriya F, Baba K, Matsuzaki N, Yuba Y, Shiraishi Y, Kanamaru H, Kuroda N, Sakata S, Takeuchi K, Yano H,
The American journal of surgical pathology. 4-Feb-2016
Anaplastic lymphoma kinase (ALK) translocation renal cell carcinomas (RCCs) have been reported by several independent groups in recent times. The clinical behavior and histopathologic characteristics of these carcinomas are not fully understood because of the paucity of cases reported. Here, we describe 2 cases of RCC harboring a novel striatin (STRN)-ALK fusion. The first case was a 33-year-old woman with no sickle cell trait who underwent nephrectomy for right renal mass and had late recurrence in para-aortic lymph nodes twice 10 and 12 years after initial surgery. After the second recurrence, she was carefully observed without any treatment. Twenty-six years after the initial nephrectomy, the second para-aortic lymphadenectomy was performed, and gastrectomy was performed for newly developed primary gastric cancer. The resected para-aortic lymph nodes were largely replaced by metastatic carcinoma. The second case was a 38-year-old man with no sickle cell trait who underwent cytoreductive nephrectomy followed by sunitinib therapy for metastatic RCC. In both cases, the tumor showed solid, papillary, tubular, and mucinous cribriform structures. Psammoma bodies were occasionally seen in the stroma. Tumor cells had a large nucleus and prominent nucleoli with predominantly eosinophilic cytoplasm. Rhabdoid cells and signet-ring cells were also observed. Intracytoplasmic mucin deposition and background mucinous stroma were confirmed. In the second case, tumor necrosis was seen in some areas. Tumor cells exhibited diffuse positive staining for ALK in both cases. ALK translocation was confirmed by fluorescent in situ hybridization, and further gene analysis revealed a STRN-ALK fusion. These cases provide great insights into ALK translocation RCCs.
Serum cartilage oligomeric matrix protein and development of radiographic and painful knee osteoarthritis. A community-based cohort of middle-aged women.Friday, February 05, 2016
Kluzek S, Bay-Jensen AC, Judge A, Karsdal MA, Shorthose M, Spector T, Hart D, Newton JL, Arden NK,
Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals. 5-Feb-2016
This study demonstrates that sCOMP levels are predictive of subsequent structural changes and incidence of painful KOA, independently of age and BMI.
MicroRNA-223 and microRNA-92a in stool and plasma samples act as complementary biomarkers to increase colorectal cancer detection.Friday, February 05, 2016
Chang PY, Chen CC, Chang YS, Tsai WS, You JF, Lin GP, Chen TW, Chen JS, Chan EC,
Oncotarget. 1-Feb-2016
Aberrant levels of circulating miRNAs are potential biomarkers for the early detection of colorectal cancer (CRC). However, no previous systematic study has examined miRNAs in various specimen types from the same patient to evaluate their clinical utility. In this study, we compiled information from ~450 articles published before 2012, and selected the 46 most frequently reported CRC-related miRNAs as candidates. We then established a 46-miRNA multiplex RT-qPCR method, and efficiently examined two clinically accessible samples: stool from fecal occult blood test and EDTA plasma. A total of 62 tissue, 447 stool, and 398 plasma samples were collected from CRC patients and healthy controls. Good correlations of detectable miRNAs were noticed in paired tumor tissues, stool, and plasma samples of 62 CRC patients. Using these 62 CRC patients and 62 matched healthy controls as the training set, 5 and 11 differentially expressed miRNAs achieved the area under the ROC curve (AUC) greater than 0.7 in stool and plasma samples, respectively. The selected miRNAs was subsequently validated using the remaining enrolled samples as the test cohort; 4 miRNAs in stool and 6 miRNAs in plasma were maintained discriminating powers for CRC patients. After examining the complementary effect, combined analysis of miR-223 and miR-92a, which were commonly present in stool and plasma samples, yielded the highest sensitivity of 96.8% and the specificity of 75% for CRC (AUC = 0.907). These results allowed us to establish a two-miRNA biosignature in two types of CRC clinical specimens with a high sensitivity for CRC detection.
Irradiation Decreases the Neuroendocrine Biomarker Pro-Opiomelanocortin in Small Cell Lung Cancer Cells In Vitro and In Vivo.Friday, February 05, 2016
Meredith SL, Bryant JL, Babur M, Riddell PW, Behrouzi R, Williams KJ, White A,
PloS one. 1-2-2016
In summary, POMC biomarker expression and secretion were reduced in SCLC tumours which regrew after irradiation and in repeatedly irradiation (irradiation-primed) cells. Therefore, POMC was no longer predictive of tumour burden. This highlights the importance of fully evaluating biomarkers during and after therapy to assess clinical utility. Furthermore, the gain in mesenchymal characteristics in irradiated cells could be indicative of a more invasive phenotype.
Developing Biosensors in Developing Countries: South Africa as a Case Study.Friday, February 05, 2016
Fogel R, Limson J,
Biosensors. 5-2-2016
A mini-review of the reported biosensor research occurring in South Africa evidences a strong emphasis on electrochemical sensor research, guided by the opportunities this transduction platform holds for low-cost and robust sensing of numerous targets. Many of the reported publications centre on fundamental research into the signal transduction method, using model biorecognition elements, in line with international trends. Other research in this field is spread across several areas including: the application of nanotechnology; the identification and validation of biomarkers; development and testing of biorecognition agents (antibodies and aptamers) and design of electro-catalysts, most notably metallophthalocyanine. Biosensor targets commonly featured were pesticides and metals. Areas  of regional import to sub-Saharan Africa, such as HIV/AIDs and tuberculosis diagnosis, are also apparent in a review of the available literature. Irrespective of the targets, the challenge to the effective deployment of such sensors remains shaped by social and economic realities such that the requirements thereof are for low-cost and universally easy to operate devices for field settings. While it is difficult to disentangle the intertwined roles of national policy, grant funding availability and, certainly, of global trends in shaping areas of emphasis in research, most notable is the strong role that nanotechnology, and to a certain extent biotechnology, plays in research regarding biosensor construction. Stronger emphasis on collaboration between scientists in theoretical modelling, nanomaterials application and or relevant stakeholders in the specific field (e.g., food or health monitoring) and researchers in biosensor design may help evolve focused research efforts towards development and deployment of low-cost biosensors.
Molecular Mechanisms of Nickel Allergy.Friday, February 05, 2016
Saito M, Arakaki R, Yamada A, Tsunematsu T, Kudo Y, Ishimaru N,
International journal of molecular sciences. 02-2-2016
Allergic contact hypersensitivity to metals is a delayed-type allergy. Although various metals are known to produce an allergic reaction, nickel is the most frequent cause of metal allergy. Researchers have attempted to elucidate the mechanisms of metal allergy using animal models and human patients. Here, the immunological and molecular mechanisms of metal allergy are described based on the findings of previous studies, including those that were recently published. In addition, the adsorption and excretion of various metals, in particular nickel, is discussed to further understand the pathogenesis of metal allergy.
Molecular Pathological Classification of Neurodegenerative Diseases: Turning towards Precision Medicine.Friday, February 05, 2016
Kovacs GG,
International journal of molecular sciences. 02-2-2016
Neurodegenerative diseases (NDDs) are characterized by selective dysfunction and loss of neurons associated with pathologically altered proteins that deposit in the human brain but also in peripheral organs. These proteins and their biochemical modifications can be potentially targeted for therapy or used as biomarkers. Despite a plethora of modifications demonstrated for different neurodegeneration-related proteins, such as amyloid-β, prion protein, tau, α-synuclein, TAR DNA-binding protein 43 (TDP-43), or fused in sarcoma protein (FUS), molecular classification of NDDs relies on detailed morphological evaluation of protein deposits, their distribution in the brain, and their correlation to clinical symptoms together with specific genetic alterations. A further facet of the neuropathology-based classification is the fact that many protein deposits show a hierarchical involvement of brain regions. This has been shown for Alzheimer and Parkinson disease and some forms of tauopathies and TDP-43 proteinopathies. The present paper aims to summarize current molecular classification of NDDs, focusing on the most relevant biochemical and morphological aspects. Since the combination of proteinopathies is frequent, definition of novel clusters of patients with NDDs needs to be considered in the era of precision medicine. Optimally, neuropathological categorizing of NDDs should be translated into in vivo detectable biomarkers to support better prediction of prognosis and stratification of patients for therapy trials.
Apobec-1 Complementation Factor (A1CF) Inhibits Epithelial-Mesenchymal Transition and Migration of Normal Rat Kidney Proximal Tubular Epithelial Cells.Friday, February 05, 2016
Huang L, Wang H, Zhou Y, Ni D, Hu Y, Long Y, Liu J, Peng R, Zhou L, Liu Z, Lyu Z, Mao Z, Hao J, Li Y, Zhou Q,
International journal of molecular sciences. 02-2-2016
Apobec-1 complementation factor (A1CF) is a member of the heterogeneous nuclear ribonucleoproteins (hnRNP) family, which participates in site-specific posttranscriptional RNA editing of apolipoprotein B (apoB) transcript. The posttranscriptional editing of apoB mRNA by A1CF in the small intestine is required for lipid absorption. Apart from the intestine, A1CF mRNA is also reported to be highly expressed in the kidneys. However, it is remained unknown about the functions of A1CF in the kidneys. The aim of this paper is to explore the potential functions of A1CF in the kidneys. Our results demonstrated that in C57BL/6 mice A1CF was weakly expressed in embryonic kidneys from E15.5dpc while strongly expressed in mature kidneys after birth, and it mainly existed in the tubules of inner cortex. More importantly, we identified A1CF negatively regulated the process of epithelial-mesenchymal transition (EMT) in kidney tubular epithelial cells. Our results found ectopic expression of A1CF up-regulated the epithelial markers E-cadherin, and down-regulated the mesenchymal markers vimentin and α-smooth muscle actin (α-SMA) in NRK52e cells. In addition, knockdown of A1CF enhanced EMT contrary to the overexpression effect. Notably, the two A1CF variants led to the similar trend in the EMT process. Taken together, these data suggest that A1CF may be an antagonistic factor to the EMT process of kidney tubular epithelial cells.
Association between IL-27 2905T/G genotypes and the risk and survival of cervical cancer: a case-control study.Friday, February 05, 2016
Wang GQ, Zhao WH, Zhao XX, Zhang J, Nan KJ,
Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals. 5-Feb-2016
Our results showed that the IL-27 2905T/G genotypes were associated with decreased the susceptibility and development of cervical cancer in Chinese Han population.
Quantitative Imaging Biomarkers of NAFLD.Friday, February 05, 2016
Kinner S, Reeder SB, Yokoo T,
Digestive diseases and sciences. 5-Feb-2016
Conventional imaging modalities, including ultrasonography (US), computed tomography (CT), and magnetic resonance (MR), play an important role in the diagnosis and management of patients with nonalcoholic fatty liver disease (NAFLD) by allowing noninvasive diagnosis of hepatic steatosis. However, conventional imaging modalities are limited as biomarkers of NAFLD for various reasons. Multi-parametric quantitative MRI techniques overcome many of the shortcomings of conventional imaging and allow comprehensive and objective evaluation of NAFLD. MRI can provide unconfounded biomarkers of hepatic fat, iron, and fibrosis in a single examination-a virtual biopsy has become a clinical reality. In this article, we will review the utility and limitation of conventional US, CT, and MR imaging for the diagnosis NAFLD. Recent advances in imaging biomarkers of NAFLD are also discussed with an emphasis in multi-parametric quantitative MRI.
Evaluating Cell Processes, Quality, and Biomarkers in Pluripotent Stem Cells Using Video Bioinformatics.Friday, February 05, 2016
Zahedi A, On V, Lin SC, Bays BC, Omaiye E, Bhanu B, Talbot P,
PloS one. 5-2-2016
There is a foundational need for quality control tools in stem cell laboratories engaged in basic research, regenerative therapies, and toxicological studies. These tools require automated methods for evaluating cell processes and quality during in vitro passaging, expansion, maintenance, and differentiation. In this paper, an unbiased, automated high-content profiling toolkit, StemCellQC, is presented that non-invasively extracts information on cell quality and cellular processes from time-lapse phase-contrast videos. Twenty four (24) morphological and dynamic features were analyzed in healthy, unhealthy, and dying human embryonic stem cell (hESC) colonies to identify those features that were affected in each group. Multiple features differed in the healthy versus unhealthy/dying groups, and these features were linked to growth, motility, and death. Biomarkers were discovered that predicted cell processes before they were detectable by manual observation. StemCellQC distinguished healthy and unhealthy/dying hESC colonies with 96% accuracy by non-invasively measuring and tracking dynamic and morphological features over 48 hours. Changes in cellular processes can be monitored by StemCellQC and predictions can be made about the quality of pluripotent stem cell colonies. This toolkit reduced the time and resources required to track multiple pluripotent stem cell colonies and eliminated handling errors and false classifications due to human bias. StemCellQC provided both user-specified and classifier-determined analysis in cases where the affected features are not intuitive or anticipated. Video analysis algorithms allowed assessment of biological phenomena using automatic detection analysis, which can aid facilities where maintaining stem cell quality and/or monitoring changes in cellular processes are essential. In the future StemCellQC can be expanded to include other features, cell types, treatments, and differentiating cells.
Fusing Data Mining, Machine Learning and Traditional Statistics to Detect Biomarkers Associated with Depression.Friday, February 05, 2016
Dipnall JF, Pasco JA, Berk M, Williams LJ, Dodd S, Jacka FN, Meyer D,
PloS one. 5-2-2016
The systematic use of a hybrid methodology for variable selection, fusing data mining techniques using a machine learning algorithm with traditional statistical modelling, accounted for missing data and complex survey sampling methodology and was demonstrated to be a useful tool for detecting three biomarkers associated with depression for future hypothesis generation: red cell distribution width, serum glucose and total bilirubin.
Diagnostics and susceptibility testing in Aspergillus.Friday, February 05, 2016
Bernal-Martínez L, Alastruey-Izquierdo A, Cuenca-Estrella M,
Future microbiology. 5-Feb-2016
Intrinsic antifungal resistance and mechanisms of secondary resistance to triazoles in A. fumigatus are also reviewed.
Gelsolin rs1078305 and rs10818524 polymorphisms were associated with risk of oral squamous cell carcinoma in a Chinese Han population.Friday, February 05, 2016
Yang XD, Zhao SF, Zhang Q, Li W, Wang YX, Hong XW, Hu QG,
Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals. 5-Feb-2016
The rs1078305 and rs10818524 SNPs of GSN were associated with increased risk for OSCC development in a Chinese Han population.
New Prognostic Biomarkers in Patients With Traumatic Brain Injury.Friday, February 05, 2016
Lorente L,
Archives of trauma research. Dec-2015
Circulating levels of some biomarkers, such as SP, sCD40L, TIMP-1, MDA, and CK-18 fragmented, related to inflammation, coagulation, oxidation, and apoptosis have been recently associated with mortality in patients with TBI. These biomarkers could help in the prognostic classification of the patients and open new research lines in the treatment of patients with TBI.
Current clinical application of serum biomarkers to detect ovarian cancer.Friday, February 05, 2016
Nowak M, Janas Ł, Stachowiak G, Stetkiewicz T, Wilczyński JR,
Przegla̜d menopauzalny = Menopause review. Dec-2015
For the last decades, hundreds of potential serum biomarkers have been assessed in diagnosing of ovarian cancer including the wide spectrum of cytokines, growth factors, adhesion molecules, proteases, hormones, coagulation factors, acute phase reactants, and apoptosis factors but except CA125 none of them have been applied to everyday clinical practice. Nowadays, the growing number of evidence suggests that the classic marker CA125 should be accompanied by HE4 and in fact, Risk of Ovarian Malignancy Algorithm (ROMA) is becoming more and more widespread in clinical practice for the evaluation of adnexal masses. Early ovarian cancer is often asymptomatic, so the challenge still exists to develop serum markers suitable for early diagnosis and screening. Current knowledge strongly points to different mechanisms of pathogenesis, genetic disturbances and clinical course of major histological subtypes of ovarian cancer. Thus, future biomarker/multimarker panels should take into consideration the implications of different molecular patterns and biological behavior of various subtypes of ovarian cancer. Very promising are studies on miRNAs - small non-protein coding gene-regulatory RNA molecules functionally involved in the pathogenesis of cancers acting as oncogenes (oncomirs) or tumor suppressors. The studies devoted to ovarian cancer tissue miRNA profiling have shown that miRNAs could be useful in diagnosing and predicting the OC outcome. They also confirmed that OC is a highly heterogeneous disease, gathering four distinct histological tumor subtypes characterized not only by distinct origin, behavior and response to chemotherapy but also by different patterns of miRNA expression.
Isolation of Circulating Tumor Cells from Multiple Epithelial Cancers with ApoStream(®) for Detecting (or Monitoring) the Expression of Folate Receptor Alpha.Friday, February 05, 2016
O'Shannessy DJ, Davis DW, Anderes K, Somers EB,
Biomarker insights. 2016
This study describes our efforts to further the field of noninvasive diagnostics, specifically in the area of liquid biopsies in oncology. We employed laser scanning cytometry using highly selective antibodies to interrogate circulating tumor cells (CTCs) that were isolated using ApoStream(®) technology to identify folate receptor alpha (FRα)-positive cells. We demonstrate that FRα(+) CTCs can be isolated from patients with metastatic cancers, including NSCLC adenocarcinoma, breast cancer, and ovarian cancer, whereas squamous cell lung cancer and normal healthy controls were devoid of FRα(+) CTCs. We believe that the developed methodology will have applications in both the diagnosis and the monitoring of FRα-expressing cancers. Folate receptor alpha (FRα) expression may have utility as a potential diagnostic and therapeutic target in solid tumors. As tissue samples are not always available for patient screening, this study evaluated a noninvasive assay in CTCs from blood samples to detect FRα expression. The presence of FRα(+) CTCs enriched using ApoStream(®) and detected using laser capture cytometry was evaluated in blood samples from cancer patients [NSCLC adenocarcinoma (n = 14), breast cancer (n = 20), ovarian cancer (n = 6), and squamous lung cancer patients (n = 6)] and healthy subjects (n = 20). The data demonstrated that FRα(+) CTCs were detected in blood from NSCLC adenocarcinoma, breast, and ovarian cancer patients, whereas squamous cell lung cancer patients and normal healthy controls lacked FRα(+) CTCs as previously known. We demonstrate that CTCs captured using ApoStream(®) can be used to detect FRα(+) CTCs and may have clinical utility as a real-time liquid biopsy for assessing FRα levels in cancer patients.
Effects of Magnesium Ascorbyl Phosphate on the Expression of Inflammatory Biomarkers after Treatment of Cultured Sebocytes with Propionibacterium acnes or Ultraviolet B Radiation.Friday, February 05, 2016
Lee WJ, Kim SL, Lee KC, Sohn MY, Jang YH, Lee SJ, Kim do W,
Annals of dermatology. Feb-2016
The prediagnostic phase of Parkinson's disease.Friday, February 05, 2016
Noyce AJ, Lees AJ, Schrag AE,
Journal of neurology, neurosurgery, and psychiatry. 11-Jan-2016
The field of prediagnostic Parkinson's disease (PD) is fast moving with an expanding range of clinical and laboratory biomarkers, and multiple strategies seeking to discover those in the earliest stages or those 'at risk'. It is widely believed that the highest likelihood of securing neuroprotective benefit from drugs will be in these subjects, preceding current point of diagnosis of PD. In this review, we outline current knowledge of the prediagnostic phase of PD, including an up-to-date review of risk factors (genetic and environmental), their relative influence, and clinical features that occur prior to diagnosis. We discuss imaging markers across a range of modalities, and the emerging literature on fluid and peripheral tissue biomarkers. We then explore current initiatives to identify individuals at risk or in the earliest stages that might be candidates for future clinical trials, what we are learning from these initiatives, and how these studies will bring the field closer to realistically commencing primary or secondary preventive trials for PD. Further progress in this field hinges on greater clinical and biological description, and understanding of the prediagnostic, peridiagnostic and immediate postdiagnostic stages of PD. Identifying subjects 3-5 years before they are currently diagnosed may be an ideal group for neuroprotective trials. At the very least, these initiatives will help clarify the stage before and around diagnosis, enabling the field to push into unchartered territory at the earliest stages of disease.
Genomic and proteomic profiling for cancer diagnosis in dogs.Friday, February 05, 2016
Morris JS,
Veterinary journal (London, England : 1997). 12-Jan-2016
Global gene expression, whereby tumours are classified according to similar gene expression patterns or 'signatures' regardless of cell morphology or tissue characteristics, is being increasingly used in both the human and veterinary fields to assist in cancer diagnosis and prognosis. Many studies on canine tumours have focussed on RNA expression using techniques such as microarrays or next generation sequencing. However, proteomic studies combining two-dimensional polyacrylamide gel electrophoresis or two-dimensional differential gel electrophoresis with mass spectrometry have also provided a wealth of data on gene expression in tumour tissues. In addition, proteomics has been instrumental in the search for tumour biomarkers in blood and other body fluids.
B7-H3, B7-H4, Foxp3 and IL-2 expression in cervical cancer: Associations with patient outcome and clinical significance.Friday, February 05, 2016
Huang C, Zhou L, Chang X, Pang X, Zhang H, Zhang S,
Oncology reports. 2-Feb-2016
The aim of this study was to determine the expression of B7-H3, B7-H4, Foxp3 and IL-2 in cervical cancer tissues, and evaluate the corresponding clinical significance. The expression of B7-H3, B7-H4, Foxp3 and IL-2 in 108 cervical cancer specimens was detected using immunohistochemistry, and their relationship with clinicopathologic parameters was determined. B7-H3, B7-H4 and Foxp3 had high levels of expression in cervical cancer cells (72.22, 80.56, and 91.56%, respectively). B7-H3 levels were only significantly associated with tumor size (P=0.013), while B7-H4, Foxp3 and IL-2 levels were significantly associated with International Federation of Gynecology and Obstetrics (FIGO) stage (P=0.023, 0.014 and 0.036, respectively) and tumor size (P=0.045, 0.010 and 0.021, respectively). Their expression levels were not correlated with age, histologic type, differentiation and lymph node metastasis (all P>0.05). Cox regression multivariate analysis confirmed that B7-H3 or B7-H4 overexpression was an independent prognostic factor. In addition, there were significant positive relationships between the expression of B7-H3 and B7-H4 with Foxp3 (P<0.001). In contrast, the expression of B7-H3 and B7-H4 was negatively correlated with IL-2 (P<0.05). B7-H3, B7-H4 and Foxp3 may be useful biomarkers in patients with cervical cancer for predicting treatment.
Precision Medicine: Personalized Proteomics for the Diagnosis and Treatment of Idiopathic Inflammatory Disease.Friday, February 05, 2016
Velez G, Roybal CN, Colgan D, Tsang SH, Bassuk AG, Mahajan VB,
JAMA ophthalmology. 4-Feb-2016
The analysis identifies a common cytokine signature for posterior uveitis and guides the diagnosis of a patient with idiopathic uveitis. Personalized treatment reversed the visual loss, illustrating how proteomic tools may individualize therapy.
Organic matter in sediment layers of an acidic mining lake as assessed by lipid analysis. Part II: Neutral lipids.Friday, February 05, 2016
Poerschmann J, Koschorreck M, Górecki T,
The Science of the total environment. 1-Feb-2016
Natural neutralization of acidic mining lakes is often limited by organic matter. The knowledge of the sources and degradability of organic matter is crucial for understanding alkalinity generation in these lakes. Sediments collected at different depths (surface sediment layer from 0 to 1 cm and deep sediment layer from 4 to 5cm) from an acidic mining lake were studied in order to characterize sedimentary organic matter based on neutral signature markers. Samples were exhaustively extracted, subjected to pre-chromatographic derivatizations and analyzed by GC/MS. Herein, molecular distributions of diagnostic alkanes/alkenes, terpenes/terpenoids, polycyclic aromatic hydrocarbons, aliphatic alcohols and ketones, sterols, and hopanes/hopanoids were addressed. Characterization of the contribution of natural vs. anthropogenic sources to the sedimentary organic matter in these extreme environments was then possible based on these distributions. With the exception of polycyclic aromatic hydrocarbons, combined concentrations across all marker classes proved higher in the surface sediment layer as compared to those in the deep sediment layer. Alkane and aliphatic alcohol distributions pointed to predominantly allochthonous over autochthonous contribution to sedimentary organic matter. Sterol patterns were dominated by phytosterols of terrestrial plants including stigmasterol and β-sitosterol. Hopanoid markers with the ββ-biohopanoid "biological" configuration were more abundant in the surface sediment layer, which pointed to higher bacterial activity. The pattern of polycyclic aromatic hydrocarbons pointed to prevailing anthropogenic input. Pyrolytic makers were likely to due to atmospheric deposition from a nearby former coal combustion facility. The combined analysis of the array of biomarkers provided new insights into the sources and transformations of organic matter in lake sediments.
Next-Generation Molecular Testing of Newborn Dried Blood Spots for Cystic Fibrosis.Friday, February 05, 2016
Lefterova MI, Shen P, Odegaard JI, Fung E, Chiang T, Peng G, Davis RW, Wang W, Kharrazi M, Schrijver I, Scharfe C,
The Journal of molecular diagnostics : JMD. 28-Jan-2016
Newborn screening for cystic fibrosis enables early detection and management of this debilitating genetic disease. Implementing comprehensive CFTR analysis using Sanger sequencing as a component of confirmatory testing of all screen-positive newborns has remained impractical due to relatively lengthy turnaround times and high cost. Here, we describe CFseq, a highly sensitive, specific, rapid (<3 days), and cost-effective assay for comprehensive CFTR gene analysis from dried blood spots, the common newborn screening specimen. The unique design of CFseq integrates optimized dried blood spot sample processing, a novel multiplex amplification method from as little as 1 ng of genomic DNA, and multiplex next-generation sequencing of 96 samples in a single run to detect all relevant CFTR mutation types. Sequence data analysis utilizes publicly available software supplemented by an expert-curated compendium of >2000 CFTR variants. Validation studies across 190 dried blood spots demonstrated 100% sensitivity and a positive predictive value of 100% for single-nucleotide variants and insertions and deletions and complete concordance across the polymorphic poly-TG and consecutive poly-T tracts. Additionally, we accurately detected both a known exon 2,3 deletion and a previously undetected exon 22,23 deletion. CFseq is thus able to replace all existing CFTR molecular assays with a single robust, definitive assay at significant cost and time savings and could be adapted to high-throughput screening of other inherited conditions.
Health care resource utilization and cost of care for haemophilia A and B patients in Iran.Friday, February 05, 2016
Gharibnaseri Z, Davari M, Cheraghali A, Eshghi P, Ravanbod R, Espandar R, Hantooshzadeh R,
Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis. 26-Jan-2016
There is an urgent need for developing clinical practice guidelines for treatment protocols, procedures and supportive care in haemophilia management in Iran.
Functional studies on circulating and disseminated tumor cells in carcinoma patients.Friday, February 05, 2016
Alix-Panabières C, Bartkowiak K, Pantel K,
Molecular oncology. 18-Jan-2016
Despite numerous clinical studies indicating the clinical relevance of circulating tumor cells (CTCs) in blood and disseminated tumor cells (DTCs) in the bone marrow of cancer patients, the functional properties of these cells are largely unknown. The focus of this review is to emphasize how functional studies on viable CTCs and DTCs can enlarge the spectrum of applications of "liquid biopsies". The low number of CTCs in the peripheral blood and DTCs in the bone marrow and the fact that carcinoma cells are difficult to culture are major challenges. Significant advances in the in vitro and in vivo expansion of CTCs and DTCs from cancer patients have been achieved, which enable us now to study the functional properties of these cells. Here, we discuss published data about functional studies on CTCs and DTCs using in vitro cultivation and in vivo xenograft models. Functional analyses on CTCs and DTCs offer the possibility to identify the metastasis-initiating cells. Moreover, CTC-derived cell lines and xenografts might point to new therapeutic targets and can be used for drug development.
Hybrid 2D-nanomaterials-based electrochemical immunosensing strategies for clinical biomarkers determination.Friday, February 05, 2016
Campuzano S, Pedrero M, Nikoleli GP, Pingarrón JM, Nikolelis DP,
Biosensors & bioelectronics. 18-Jan-2016
Owing to the outstanding conductivity and biocompatibility as well as numerous other fascinating properties of two-dimensional (2D)-nanomaterials, 2D-based nanohybrids have shown unparalleled superiorities in the field of electrochemical biosensors. This review highlights latest advances in electrochemical immunosensors for clinical biomarkers based on different hybrid 2D-nanomaterials. Particular attention will be given to hybrid nanostructures involving graphene and other graphene-like 2D-layered nanomaterials (GLNs). Several recent strategies for using such 2D-nanomaterial heterostructures in the development of modern immunosensors, both for tagging or modifying electrode transducers, are summarized and discussed. These hybrid nanocomposites, quite superior than their rival materials, will undoubtedly have an important impact within the near future and not only in clinical areas. Current challenges and future perspectives in this rapidly growing field are also outlined.
MicroRNA expression pattern in pre-eclampsia (Review).Friday, February 05, 2016
Jairajpuri DS, Almawi WY,
Molecular medicine reports. 2-Feb-2016
Pre-eclampsia (PE), a pregnancy complication, is a leading cause of maternal and fetal morbidity and mortality. Although its exact etiology and pathogenesis remain elusive, PE results from an interaction of inherited and non‑inherited factors. The clinical symptoms of PE appear post‑mid‑stage of gestation and, at present, there are no early signs/markers for its onset and progression. MicroRNAs function as gene regulators, and are involved in development and pathology. A burgeoning number of studies have highlighted microRNAs as potential biomarkers for minimal invasive assessment. However, it remains a matter of debate as to which microRNA type is involved in PE onset and progression, as well as the clinical utility of testing for these species. In the present review, we have summarized the latest findings on the association of PE with the aberrant expression of placental microRNAs; in particular, those that are detectable in the blood. The current understanding of the mechanisms of microRNA‑target gene interactions that underpin the involvement of microRNAs in the pathogenesis of PE is also discussed.
Bevacizumab and temozolomide versus temozolomide alone as neoadjuvant treatment in unresected glioblastoma: the GENOM 009 randomized phase II trial.Friday, February 05, 2016
Balana C, De Las Penas R, Sepúlveda JM, Gil-Gil MJ, Luque R, Gallego O, Carrato C, Sanz C, Reynes G, Herrero A, Ramirez JL, Pérez-Segura P, Berrocal A, Vieitez JM, Garcia A, Vazquez-Estevez S, Peralta S, Fernandez I, Henriquez I, Martinez-Garcia M, De la Cruz JJ, Capellades J, Giner P, Villà S,
Journal of neuro-oncology. 3-Feb-2016
We sought to determine the impact of bevacizumab on reduction of tumor size prior to chemoradiotherapy in unresected glioblastoma patients. Patients were randomized 1:1 to receive temozolomide (TMZ arm) or temozolomide plus bevacizumab (TMZ + BEV arm). In both arms, neoadjuvant treatment was temozolomide (85 mg/m(2), days 1-21, two 28-day cycles), concurrent radiation plus temozolomide, and six cycles of adjuvant temozolomide. In the TMZ + BEV arm, bevacizumab (10 mg/kg) was added on days 1 and 15 of each neoadjuvant cycle and on days 1, 15 and 30 of concurrent treatment. The primary endpoint was investigator-assessed response to neoadjuvant treatment. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and the impact on outcome of MGMT methylation in tumor and serum. One hundred and two patients were included; 43 in the TMZ arm and 44 in the TMZ + BEV arm were evaluable for response. Results favored the TMZ + BEV arm in terms of objective response (3 [6.7 %] vs. 11 [22.9 %]; odds ratio 4.2; P = 0.04). PFS and OS were longer in the TMZ + BEV arm, though the difference did not reach statistical significance. MGMT methylation in tumor, but not in serum, was associated with outcome. More patients experienced toxicities in the TMZ + BEV than in the TMZ arm (P = 0.06). The combination of bevacizumab plus temozolomide is more active than temozolomide alone and may well confer benefit in terms of tumor shrinkage in unresected patients albeit at the expense of greater toxicity.
Hepatic Transporter Expression in Metabolic Syndrome: Phenotype, serum metabolic hormones, and transcription factor expression.Friday, February 05, 2016
Donepudi AC, Cheng Q, Lu ZJ, Cherrington NJ, Slitt AL,
Drug metabolism and disposition: the biological fate of chemicals. 4-Feb-2016
Obesity is a complex and multifactorial disease, associated with increased body weight, insulin resistance, diabetes, and the alteration of multiple metabolic hormones. Obesity rates have increased worldwide, which increases the need to understand how this population will respond to drugs and chemicals of exposure. The purpose of this study was to determine the ontogeny of clinical biomarkers such as serum hormone levels, blood glucose levels and physiological markers that correlate with nuclear receptor and transporter-related pathways in lean and obese mice. Livers from male and female WT (C57BL/6) and ob/ob mice littermates were collected before, during, and after the onset of obesity. Serum hormone and mRNA levels were analyzed. Physiological changes and gene expression during maturation and progression to obesity was performed using canonical correlations. Significant ontogenic changes in both WT and ob/ob mice were observed and these ontogenic changes differ in ob/ob mice with the development of obesity. In males and females, the ontogenic pattern of genes such as Abcc3, 4, Abcg2, Cyp2b10 and 4a14 expression started to differ from week 3, and became significant at week 4 and 8 in ob/ob mice compared to WT mice. Serum glucose levels, body and liver weights showed high correlation with change in hepatic gene expression during the development of obesity. In obese males, serum resistin, glucagon and glucose levels correlated with the expression of most hepatic Abc transporters, whereas in obese females, serum GLP-1 levels are correlated with most hepatic uptake transporters and Cyp enzymes. Overall, the correlation between physiological changes and gene expression indicate that metabolism-related hormones may play a role in regulating the genes involved in drug metabolism and transport.
Arginine ADP-ribosyltransferase 1 promotes angiogenesis in colorectal cancer via the PI3K/Akt pathway.Friday, February 05, 2016
Yang L, Xiao M, Li X, Tang Y, Wang YL,
International journal of molecular medicine. 29-Jan-2016
Arginine adenosine diphosphate (ADP)-ribosyl-transferase 1 (ART1) is known to play an important role in many physiological and pathological processes. Previous studies have demonstrated that ART1 promotes proliferation, invasion and metastasis in colon carcinoma. However, it was unclear whether ART1 is involved in angiogenesis in cases of colorectal cancer (CRC). In the present study, lentiviral vector‑mediated ART1‑cDNA or ART1-shRNA were transfected into LoVo cells, and the LoVo cells transfected with ART1-cDNA or ART1-shRNA were co-cultured with human umbilical vein endothelial cells (HUVECs) to determine the influence of ART1 on HUVECs. The proliferation, migration and angiogenesis of HUVECs were monitored using a cell counting kit-8 assay, a Transwell migration assay and immunohistochemical analysis in intrasplenic allograft tumors, respectively. Hypoxia‑inducible factor 1-α (HIF-1α), total (t-)Akt, phosphorylated (p-)Akt, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) expression levels were detected via western blot analysis. Our results revealed that HUVECs which were co-cultured with ART1-cDNA LoVo cells showed higher proliferation, migration and angiogenic abilities, but a reduction was noted in those cultured with ART1-shRNA LoVo cells; p-Akt, HIF-1α, VEGF and bFGF expression was increased in HUVECs cultured with ART1‑cDNA-transfected LoVo cells, but reduced in ART1-shRNA-transfected LoVo cells. In a mouse xenograft model, we noted that the tumor microvessel density (MVD) was significantly increased in intrasplenic transplanted ART1‑cDNA CT26 tumors but decreased in intrasplenic transplanted ART1‑shRNA tumors. These data suggest that ART1 promoted the expression of HIF-1α via the Akt pathway in tumor cells. It also upregulated VEGF and bFGF and enhanced angiogenesis in HUVECs. Thus, we suggest that ART1 plays an important role in the invasion of CRC cells and the metastasis of CRC.
miR-137 acts as a tumor suppressor in papillary thyroid carcinoma by targeting CXCL12.Friday, February 05, 2016
Dong S, Jin M, Li Y, Ren P, Liu J,
Oncology reports. 1-Feb-2016
Accumulating evidence has shown that aberrantly expressed microRNAs (miRs) are extensively involved in tumorigenesis. microRNA-137 (miR-137) has been reported as a tumor suppressor in various types of cancer. However, the biological function and underlying molecular mechanism of miR-137 in papillary thyroid carcinoma (PTC) remain largely unknown. Therefore, the present study aimed to investigate the expression pattern of miR-137 and its functional significance in PTC. Quantitative RT-PCR (qRT-PCR) assay showed that miR-137 expression was significantly downregulated in human PTC tissues, and its expression was significantly negatively correlated with tumor-node-metastasis (TNM) stage and lymph node metastasis. Functional assays showed that forced expression of miR-137 in PTC cells significantly inhibited proliferation, colony formation, migration and invasion in vitro. Importantly, on the basis of bioinformatic analysis and luciferase reporter assay, we found that miR-137 directly targeted the 3'-untranslated region (3'-UTR) of C-X-C motif chemokine 12 (also known as SDF-1) (CXCL12). qRT-PCR and western blot analysis further verified the results and demonstrated that miR-137 could downregulate CXCL12 expression in PTC cells. We also confirmed that CXCL12 expression was increased in PTC tissues and was inversely correlated with miR-137. In addition, our results also showed that downregulation of CXCL12 mimicked the effects of miR-137 overexpression, and upregulation of CXCL12 partially reversed the inhibitory effects of miR-137 in PTC cells. These results showed that miR-137 may function as a tumor suppressor in PTC by targeting CXCL12, suggesting that miR-137 may act as a potential target for PTC treatment.
KCTD12 Regulates Colorectal Cancer Cell Stemness through the ERK Pathway.Friday, February 05, 2016
Li L, Duan T, Wang X, Zhang RH, Zhang M, Wang S, Wang F, Wu Y, Huang H, Kang T,
Scientific reports. 2016
Targeting cancer stem cells (CSCs) in colorectal cancer (CRC) remains a difficult problem, as the regulation of CSCs in CRC is poorly understood. Here we demonstrated that KCTD12, potassium channel tetramerization domain containing 12, is down-regulated in the CSC-like cells of CRC. The silencing of endogenous KCTD12 and the overexpression of ectopic KCTD12 dramatically enhances and represses CRC cell stemness, respectively, as assessed in vitro and in vivo using a colony formation assay, a spheroid formation assay and a xenograft tumor model. Mechanistically, KCTD12 suppresses CRC cell stemness markers, such as CD44, CD133 and CD29, by inhibiting the ERK pathway, as the ERK1/2 inhibitor U0126 abolishes the increase in expression of CRC cell stemness markers induced by the down-regulation of KCTD12. Indeed, a decreased level of KCTD12 is detected in CRC tissues compared with their adjacent normal tissues and is an independent prognostic factor for poor overall and disease free survival in patients with CRC (p = 0.007). Taken together, this report reveals that KCTD12 is a novel regulator of CRC cell stemness and may serve as a novel prognostic marker and therapeutic target for patients with CRC.
Bioinformatics analysis of molecular mechanisms involved in intervertebral disc degeneration induced by TNF‑α and IL‑1β.Friday, February 05, 2016
Xu F, Gao F, Liu Y, Wang Z, Zhuang X, Qu Z, Ma H, Liu Y, Fu C, Zhang Q, Duan X,
Molecular medicine reports. 4-Feb-2016
The present study aimed to explore the molecular mechanisms associated with intervertebral disc degeneration (IDD) induced by tumor necrosis factor (TNF)‑α and interleukin (IL)‑1β. The microarray dataset no. GSE42611 was downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) between four experimental nucleus pulposus samples and four control nucleus pulposus samples were analyzed. Subsequently, Gene Ontology (GO) and pathway enrichment analyses of DEGs were performed, followed by protein‑protein interaction (PPI) network construction and prediction of a regulatory network of transcription factor (TFs). Finally, the transcriptional regulatory network was integrated into the PPI network to analyze the network modules. A total of 246 upregulated and 290 downregulated DEGs were identified. The upregulated DEGs were mainly associated with GO terms linked with inflammatory response and apoptotic pathways, while the downregulated DEGs were mainly associated with GO terms linked with cell adhesion and pathways of extracellular matrix ‑ receptor interaction. In the PPI network, IL6, COL1A1, NFKB1 and HIF1A were hub genes, and in addition, NFKB1 and HIF1A were TFs. Pathways of apoptosis and extracellular matrix ‑ receptor interaction may have important roles in IDD progression. IL6, COL1A1 and the TFs NFKB1 and HIF1A may be used as biomarkers for IDD diagnosis and treatment.
Effect of EGFR and p-AKT Overexpression on Chromosomal Instability in Gastric Cancer.Friday, February 05, 2016
Hisamatsu Y, Oki E, Otsu H, Ando K, Saeki H, Tokunaga E, Aishima S, Morita M, Oda Y, Maehara Y,
Annals of surgical oncology. 4-Feb-2016
Our data showed that both EGFR and p-AKT overexpression were clearly associated with DNA aneuploidy. Aneuploidy could be a useful marker for therapies that target EGFR.
Analysis of Clinical and Molecular Factors Impacting Oncologic Outcomes in Undifferentiated Pleomorphic Sarcoma.Friday, February 05, 2016
Roland CL, May CD, Watson KL, Al Sannaa GA, Dineen SP, Feig R, Landers S, Ingram DR, Wang WL, Ashleigh Guadagnolo B, Feig B, Hunt KK, Cormier JN, Lazar AJ, Torres KE,
Annals of surgical oncology. 3-Feb-2016
Loss of cyclin D1, overexpression of AXL, and loss of PTEN are associated with poor cancer-specific outcomes and warrant further investigation in UPS. The differences in protein expression in sporadic versus RA-UPS may indicate that the activated molecular signaling nodes may be different for each specific histology and also could explain the aggressive phenotype seen in RA-UPS compared with the sporadic lesions.
Cell-Free DNA as a Diagnostic Tool for Human Parasitic Infections.Friday, February 05, 2016
Weerakoon KG, McManus DP,
Trends in parasitology. 1-Feb-2016
Parasites often cause devastating diseases and represent a significant public health and economic burden. More accurate and convenient diagnostic tools are needed in support of parasite control programmes in endemic regions, and for rapid point-of-care diagnosis in nonendemic areas. The detection of cell-free DNA (cfDNA) is a relatively new concept that is being applied in the current armamentarium of diagnostics. Here, we review the application of cfDNA detection with nucleic acid amplification tests for the diagnosis and evaluation of different human parasitic infections and highlight the significant benefits of the approach using non-invasive clinical samples.
PET imaging of epidermal growth factor receptor expression in tumours using 89Zr-labelled ZEGFR:2377 affibody molecules.Friday, February 05, 2016
Garousi J, Andersson KG, Mitran B, Pichl ML, Ståhl S, Orlova A, Löfblom J, Tolmachev V,
International journal of oncology. 2-Feb-2016
Epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase receptor, which is overexpressed in many types of cancer. The use of EGFR-targeting monoclonal antibodies and tyrosine-kinase inhibitors improves significantly survival of patients with colorectal, non-small cell lung cancer and head and neck squamous cell carcinoma. Detection of EGFR overexpression provides important prognostic and predictive information influencing management of the patients. The use of radionuclide molecular imaging would enable non-invasive repeatable determination of EGFR expression in disseminated cancer. Moreover, positron emission tomography (PET) would provide superior sensitivity and quantitation accuracy in EGFR expression imaging. Affibody molecules are a new type of imaging probes, providing high contrast in molecular imaging. In the present study, an EGFR-binding affibody molecule (ZEGFR:2377) was site-specifically conjugated with a deferoxamine (DFO) chelator and labelled under mild conditions (room temperature and neutral pH) with a positron-emitting radionuclide 89Zr. The 89Zr-DFO-ZEGFR:2377 tracer demonstrated specific high affinity (160±60 pM) binding to EGFR-expressing A431 epidermoid carcinoma cell line. In mice bearing A431 xenografts, 89Zr-DFO-ZEGFR:2377 demonstrated specific uptake in tumours and EGFR-expressing tissues. The tracer provided tumour uptake of 2.6±0.5% ID/g and tumour-to-blood ratio of 3.7±0.6 at 24 h after injection. 89Zr-DFO-ZEGFR:2377 provides higher tumour-to-organ ratios than anti-EGFR antibody 89Zr-DFO-cetuximab at 48 h after injection. EGFR‑expressing tumours were clearly visualized by microPET using 89Zr-DFO-ZEGFR:2377 at both 3 and 24 h after injection. In conclusion, 89Zr-DFO-ZEGFR:2377 is a potential probe for PET imaging of EGFR-expression in vivo.
Neuron specific enolase: a promising therapeutic target in acute spinal cord injury.Friday, February 05, 2016
Haque A, Ray SK, Cox A, Banik NL,
Metabolic brain disease. 5-Feb-2016
Enolase is a multifunctional protein, which is expressed abundantly in the cytosol. Upon stimulatory signals, enolase can traffic to cell surface and contribute to different pathologies including injury, autoimmunity, infection, inflammation, and cancer. Cell-surface expression of enolase is often detected on activated macrophages, microglia/macrophages, microglia, and astrocytes, promoting extracellular matrix degradation, production of pro-inflammatory cytokines/chemokines, and invasion of inflammatory cells in the sites of injury and inflammation. Inflammatory stimulation also induces translocation of enolase from the cytosolic pool to the cell surface where it can act as a plasminogen receptor and promote extracellular matrix degradation and tissue damage. Spinal cord injury (SCI) is a devastating debilitating condition characterized by progressive pathological changes including complex and evolving molecular cascades, and insights into the role of enolase in multiple inflammatory events have not yet been fully elucidated. Neuronal damage following SCI is associated with an elevation of neuron specific enolase (NSE), which is also known to play a role in the pathogenesis of hypoxic-ischemic brain injury. Thus, NSE is now considered as a biomarker in ischemic brain damage, and it has recently been suggested to be a biomarker in traumatic brain injury (TBI), stroke and anoxic encephalopathy after cardiac arrest and acute SCI as well. This review article gives an overview of the current basic research and clinical studies on the role of multifunctional enolase in neurotrauma, with a special emphasis on NSE in acute SCI.
Higher augmentation index is associated with tension-type headache and migraine in middle-aged/older humans with obesity.Friday, February 05, 2016
Kalil GZ, Recober A, Hoang-Tienor A, Bridget Zimmerman M, Haynes WG, Pierce GL,
Obesity (Silver Spring, Md.). 5-Feb-2016
Increased aortic AI but not stiffness is associated with TTH and migraine among middle-aged/older adults with obesity and high CVD risk.
Frequency of chromosome 17 polysomy in relation to CEP17 copy number in a large breast cancer cohort.Friday, February 05, 2016
Koudelakova V, Trojanec R, Vrbkova J, Donevska S, Bouchalova K, Kolar Z, Varanasi L, Hajduch M,
Genes, chromosomes & cancer. 5-Feb-2016
Eligibility to anti-HER2 therapy for breast tumors strictly depends on demonstrating HER2 overexpression (by immunohistochemistry) or HER2 gene amplification by in situ hybridization (ISH), usually defined by the ratio of HER2 gene to chromosome 17 centromere (CEP17) copies. However, the CEP17 copy number increase (CNI) has been proven responsible for misleading HER2 FISH results and recent small cohort studies suggest that chromosome 17 polysomy is actually very rare. Here we investigated by FISH the frequency of true chromosome 17 polysomy in a consecutive cohort of 5,477 invasive breast cancer patients. We evaluated and selected the LSI 17p11.2 probe for chromosome 17 enumeration on a training cohort of 67 breast cancer samples (CEP17 ≥ 2.5). LSI 17p11.2 was used in the 297/5,477 patients from the validation cohort displaying CEP17 CNI (CEP17 ≥ 3.0). Using HER2/17p11.2 scoring criteria, 37.3%/1.5% patients initially classified as equivocal/non-amplified were reclassified as amplified. For a more accurate assessment of chromosome 17 and ploidy in the samples, we tested six markers located on chromosome 17 and centromeric regions of chromosome 8 (CEP8) and 11 (CEP11) in 67 patients with CEP17 and LSI 17p11.2 CNI. True polysomy (hyperdiploidy) according to these markers was found in 0.48% of cases (24/5,020). CEP8 and CEP11 CNI (≥3.0) was more frequent in the hyperdiploid than CEP17 non-polysomic group (55.6% vs. 6.1% and 25% vs. 2.3%, respectively). Our results suggest that chromosome 17 polysomy is a rare event found in <1% breast cancer cases and that polysomy of other chromosomes frequently occurs with chromosome 17 polysomy. © 2015 Wiley Periodicals, Inc.
Systemic inflammatory cytokine analysis to monitor biomaterial augmented tissue healing.Friday, February 05, 2016
Bryan N, Ashwin H, Smart N, Weyhe D, Wohlert S, Bayon Y, Hunt JA,
The International journal of artificial organs. 2-Feb-2016
Analysis of systemic inflammation biomarkers confirmed inflammation elicited by surgeries and meshes irrespective of their composition. However, at an early postoperative endpoint (i.e., 1 week), some biomarkers, namely, IL-18 and RANTES, appeared to discriminate the noncomposite mesh from the composite materials, although in this study all materials successfully repaired the defects without recurrence or external indicators of postoperative chronic pain.
Glucose tolerance and cardiovascular risk biomarkers in non-diabetic non-obese obstructive sleep apnea patients: Effects of long-term continuous positive airway pressure.Friday, February 05, 2016
Monneret D, Tamisier R, Ducros V, Faure P, Halimi S, Baguet JP, Lévy P, Pépin JL, Borel AL,
Respiratory medicine. 28-Jan-2016
In non-obese non-diabetic OSA patients, nocturnal oxygen desaturation is strongly associated to insulin resistance. LT-CPAP does not improve glucose homeostasis nor insulin sensitivity but has a favorable effect on antioxidant capacity and cardiovascular risk biomarkers.
Profile of oxidative stress markers is dependent on vitamin D levels in patients with chronic hepatitis C.Friday, February 05, 2016
Sales de Almeida JP, Liberatti LS, Nascimento Barros FE, Kallaur AP, Batisti Lozovoy MA, Scavuzzi BM, Panis C, Reiche EM, Dichi I, Colado Simão AN,
Nutrition (Burbank, Los Angeles County, Calif.). Mar-2016
Vitamin D insufficiency contributes to the inflammatory process and oxidative stress imbalance in patients with HCV. The profile of oxidative stress markers in these patients depends on vitamin D levels, which probably change intracellular signalling pathways and increase inflammation and liver injury.
Transgelin increases metastatic potential of colorectal cancer cells in vivo and alters expression of genes involved in cell motility.Friday, February 05, 2016
Zhou HM, Fang YY, Weinberger PM, Ding LL, Cowell JK, Hudson FZ, Ren M, Lee JR, Chen QK, Su H, Dynan WS, Lin Y,
BMC cancer. 2015
Increases or decreases in transgelin levels have reciprocal effects on tumor cell behavior, with higher expression promoting metastasis. Chronic overexpression influences steady-state levels of mRNAs for metastasis-related genes.
Zapotin (5,6,2',6'-tetramethoxyflavone) modulates the crosstalk between autophagy and apoptosis pathways in cancer cells with overexpressed constitutively active PKCϵ.Friday, February 05, 2016
Toton E, Romaniuk A, Budzianowski J, Hofmann J, Rybczynska M,
Nutrition and cancer. 4-Feb-2016
Autophagy is important in the regulation of survival and death signaling pathways in cancer. PKCϵ revealed high transforming potential and the ability to increase cell migration, invasion, and metastasis. Zapotin (5,6,2',6'-tetramethoxyflavone), a natural flavonoid, showed chemopreventive and anticancer properties. Previously, we reported that downmodulation of induced PKCϵ level by zapotin was associated with decreased migration and increased apoptosis in HeLa cell line containing doxycycline-inducible constitutively active PKCϵ (PKCϵA/E, Ala(159) → Glu). Depending on the genetic and environmental content of cells, autophagy may either precede apoptosis or occur simultaneously. The purpose of this study was to assess the effect of zapotin on autophagy. Increasing concentration of zapotin (from 7.5 µM to 30 µM) caused an inhibition of the formation of autophagosomes and a decline in microtubule-associated protein 1 light chain 3 (LC3) protein levels. The gene expression level of major negative regulator of autophagy was noticeably increased. Moreover, the expression of the pivotal autophagy genes was decreased. These changes were accompanied by alternation in autophagy-related protein levels. In conclusion, our results implied that both the antiautophagic and the proapoptosis effect of zapotin in HeLaPKCϵA/E cells are associated with the protein kinase C epsilon signaling pathway and lead to programmed cell death.
Use of metabolomics for the chemotaxonomy of legume-associated Ascochyta and allied genera.Friday, February 05, 2016
Kim W, Peever TL, Park JJ, Park CM, Gang DR, Xian M, Davidson JA, Infantino A, Kaiser WJ, Chen W,
Scientific reports. 2016
Chemotaxonomy and the comparative analysis of metabolic features of fungi have the potential to provide valuable information relating to ecology and evolution, but have not been fully explored in fungal biology. Here, we investigated the chemical diversity of legume-associated Ascochyta and Phoma species and the possible use of a metabolomics approach using liquid chromatography-mass spectrometry for their classification. The metabolic features of 45 strains including 11 known species isolated from various legumes were extracted, and the datasets were analyzed using chemometrics methods such as principal component and hierarchical clustering analyses. We found a high degree of intra-species consistency in metabolic profiles, but inter-species diversity was high. Molecular phylogenies of the legume-associated Ascochyta/Phoma species were estimated using sequence data from three protein-coding genes and the five major chemical groups that were detected in the hierarchical clustering analysis were mapped to the phylogeny. Clusters based on similarity of metabolic features were largely congruent with the species phylogeny. These results indicated that evolutionarily distinct fungal lineages have diversified their metabolic capacities as they have evolved independently. This whole metabolomics approach may be an effective tool for chemotaxonomy of fungal taxa lacking information on their metabolic content.
[The significance of biobanks for clinical development].Friday, February 05, 2016
Thomas M, Kiermaier A, Cannarile M,
Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz. 4-Feb-2016
Access to samples in biobanks and collection of samples for evaluation of biomarkers in clinical trials are an essential basis for the identification and development of biomarkers. From the perspective of a research-based pharmaceutical company identification of biomarkers and the accompanying diagnostics are an essential prerequisite for the further evolution of personalised healthcare-and the key to more effective and efficient healthcare. Research-based pharmaceutical companies can basically use four types of biobanks: biobanks of university hospitals, commercial providers, collaborative groups and company-owned biobanks. Areas of application, arising from the use of biobanks in the context of clinical development, are collection of prevalence data, evaluation of biomarker stability in different disease stages, technical validation of assays, an optimized course of clinical studies by focusing on defined, biomarker-stratified groups of patients and pharmacogenetic research. Challenges are, in particular, the availability of clinically annotated samples and tissue matching blood samples, in addition to sample quality, number and amount. An acceptable legal and regulatory framework, as well as the positive perception of biomarker data by politicians and the public, are important prerequisites for translational research for identification of biomarkers in clinical studies. Also, the early establishment of research alliances between academia and the pharmaceutical industry are required to transfer research results in new strategies for prevention, diagnosis and treatment of patients.
Prognostic Value of Serial Changes in High-Sensitivity Cardiac Troponin I and T over 3 Months Using Reference Change Values in Hemodialysis Patients.Friday, February 05, 2016
Sandoval Y, Herzog CA, Love SA, Cao J, Hu Y, Wu AH, Gilbertson D, Brunelli SM, Young A, Ler R, Apple FS,
Clinical chemistry. 4-Feb-2016
Changes over 3 months in hs-cTnI and hs-cTnT of >RCV identified patients at greater risk of all-cause mortality, and for hs-cTnI were also predictive of SCD. Among patients with middle tertile cardiac troponin concentrations, hs-cTnI changes >RCV provided additive prognostic value for both SCD and all-cause mortality, whereas those for hs-cTnT provided additive prognostic value only for all-cause mortality.
Haplo-insufficiency of both BubR1 and SGO1 accelerates cellular senescence.Friday, February 05, 2016
Park SH, Xie S, Rao CV, Dai W,
Journal of hematology & oncology. 2016
Taken together, our observations suggest that combined deficiency of BubR1 and Sgo1 accelerates cellular senescence.
Analytical and clinical comparison of different immunoassay systems for the detection of antiphospholipid antibodies.Friday, February 05, 2016
Montaruli B, De Luna E, Erroi L, Marchese C, Mengozzi G, Napoli P, Nicolo' C, Romito A, Bertero MT, Sivera P, Migliardi M,
International journal of laboratory hematology. 5-Feb-2016
By guidelines, all laboratories are strongly advised to validate/verify the manufacturer's cutoff values. We recommend establishing low-positive, medium-/high-positive, and high-positive CliA IgG aCL and a-β2GpI ranges in order to help clinicians in the diagnosis and treatment of APS.
Modulation of Endothelial Injury Biomarkers by Traditional Chinese Medicine LC in Systemic Lupus Erythematosus Patients Receiving Standard Treatments.Friday, February 05, 2016
Chang HH, Luo SF, Hsue YT, Chang CM, Lee TY, Huang YC, Hsu ML, Chen YJ,
Scientific reports. 2016
LC is an herbal remedy effectively reduced therapeutic dosage of glucocorticoid for systemic lupus erythematosus (SLE) patients in clinical trial (ISRCTN81818883). This translational research examined the impact of LC on biomarkers of endothelial injury in the enrolled subjects. Fifty seven patients with SLE were randomized to receive standard treatment without or with LC supplements. Blood samples were taken serially for quantification of endothelial progenitor cells (EPCs), circulating endothelial cells (CECs) and serological factors. The proportion of EPCs in the placebo group continued to increase during trial and was further elevated after withdrawal of standard treatment. The EPC ratio of LC group remained stationary during the entire observation period. The CEC ratio in placebo group exhibited an increasing trend whereas that in LC group declined. The ratio of apoptotic CECs had an increasing trend in both groups, to a lesser extent in LC group. After treatment, the levels of VEGF and IL-18 have a trend declined to a level lower in the LC group than the placebo group. No significant alteration was noted in serum levels of IFN-α, IL-1β and IL-6. The reduction of the steroid dosage by adding LC might be correlated with less extensive endothelial injury in SLE patients.
Analysis of the expression and localization of tight junction transmembrane proteins, claudin-1, -4, -7, occludin and JAM-A, in human cervical adenocarcinoma.Friday, February 05, 2016
Akimoto T, Takasawa A, Murata M, Kojima Y, Takasawa K, Nojima M, Aoyama T, Hiratsuka Y, Ono Y, Tanaka S, Osanai M, Hasegawa T, Saito T, Sawada N,
Histology and histopathology. 5-Feb-2016
As expected, there were immunohistochemical differences between cervical adenocarcinoma and non-neoplastic cervical glands by using antibodies against tight junction transmembrane proteins. These results suggest that CLDN-1 and JAM-A are potential biomarkers for cervical adenocarcinoma.
Diagnostically important muscle pathology in DNAJB6 mutated LGMD1D.Friday, February 05, 2016
Sandell S, Huovinen S, Palmio J, Raheem O, Lindfors M, Zhao F, Haapasalo H, Udd B,
Acta neuropathologica communications. 2016
Since DNAJB6 is known to interact with members of the chaperone assisted selective autophagy complex (CASA), including BAG3 - a known myofibrillar myopathy causing gene, the molecular muscle pathology is apparently mediated through impaired functions of CASA and possibly other complexes needed for the maintenance of the Z-disk and sarcomeric structures. The corresponding findings on histopathology offer clues for the diagnosis.
Salivary biomarkers for detection of oral squamous cell carcinoma in a Taiwanese population.Friday, February 05, 2016
Gleber-Netto FO, Yakob M, Li F, Feng Z, Dai J, Kao HK, Chang YL, Chang KP, Wong DT,
Clinical cancer research : an official journal of the American Association for Cancer Research. 4-Feb-2016
Combination of transcriptomic and proteomic salivary markers is of great value for oral cancer detection and differentiation from PMOD patients and controls.
MET amplification and exon 14 splice site mutation define unique molecular subgroups of Non-small Cell Lung Carcinoma with poor prognosis.Friday, February 05, 2016
Tong JH, Yeung SF, Chan AW, Chung LY, Chau SL, Lung RW, Tong CY, Chow C, Tin EK, Yu YH, Li H, Pan Y, Chak WP, Ng CS, Mok TS, To KF,
Clinical cancer research : an official journal of the American Association for Cancer Research. 4-Feb-2016
The high incidence of MET∆14 mutation in sarcomatoid carcinoma suggested that MET inhibition may benefit this specific subgroup of patients.
Longitudinal copy number, whole exome and targeted deep sequencing of 'good risk' IGHV-mutated CLL patients with progressive disease.Friday, February 05, 2016
Rose-Zerilli MJ, Gibson J, Wang J, Tapper W, Davis Z, Parker H, Larrayoz M, McCarthy H, Walewska R, Forster J, Gardiner A, Steele AJ, Chelala C, Ennis S, Collins A, Oakes C, Oscier DG, Strefford JC,
Leukemia. 5-Feb-2016
Disease progression in IGHV-M CLL with 'good-risk' cytogenetics is frequently associated with co-evolution of 'poor risk' driver mutations and DNA methylation changes.Drug resistance in IGHV-M CLL may be consequent upon the emergence of an IGHV-U cloneThe biological features of IGHV-M CLL responsible for disease progression are still poorly understood. We undertook a longitudinal study close to diagnosis, pre-treatment and post relapse in thirteen patients presenting with cMBL or Stage A disease and good risk biomarkers (IGHV-M genes, no del(17p) or del(11q) and low CD38 expression) who nevertheless developed progressive disease, of whom ten have required therapy. Using cytogenetics, FISH, genome-wide DNA methylation and copy number analysis together with whole exome, targeted deep- and Sanger sequencing, at diagnosis we identified mutations in established CLL driver genes in nine (69%), non-coding mutations (PAX5 enhancer region) in three, and genomic complexity in two patients. Branching evolutionary trajectories predominated (n=9/13), revealing intra-tumoural epi- and genetic heterogeneity and sub-clonal competition prior to therapy. Of the patients subsequently requiring treatment, two had sub-clonal TP53 mutations that would not be detected by standard methodologies, three qualified for the very-low risk category defined by integrated mutational and cytogenetic analysis and yet had established or putative driver mutations and one patient developed progressive, therapy-refractory disease associated with the emergence of an IGHV-U clone. These data suggest that extended genomic and immunogenetic screening may have clinical utility in patients with apparent good risk disease.Leukemia accepted article preview online, 05 February 2016. doi:10.1038/leu.2016.10.
Molecular subtype profiling of invasive breast cancers weakly positive for estrogen receptor.Friday, February 05, 2016
Sheffield BS, Kos Z, Asleh-Aburaya K, Wang XQ, Leung S, Gao D, Won J, Chow C, Rachamadugu R, Stijleman I, Wolber R, Gilks CB, Myles N, Thomson T, Hayes MM, Bernard PS, Nielsen TO, Chia SK,
Breast cancer research and treatment. 4-Feb-2016
The estrogen receptor (ER) is a key predictive biomarker in the treatment of breast cancer. There is uncertainty regarding the use of hormonal therapy in the setting of weakly positive ER by immunohistochemistry (IHC). We report intrinsic subtype classification on a cohort of ER weakly positive early-stage breast cancers. Consecutive cases of breast cancer treated by primary surgical resection were retrospectively identified from 4 centers that engage in routine external proficiency testing for breast biomarkers. ER-negative (Allred 0 and 2) and ER weakly positive (Allred 3-5) cases were included. Gene expression profiling was performed using qRT-PCR. Intrinsic subtype prediction was made based upon the PAM50 gene expression signature. 148 cases were included in the series: 60 cases originally diagnosed as ER weakly positive and 88 ER negative. Of the cases originally assessed as ER weakly positive, only 6 (10 %) were confirmed to be of luminal subtype by gene expression profiling; the remaining 90 % of cases were classified as basal-like or HER2-enriched subtypes. This was not significantly different than the fraction of luminal cases identified in the IHC ER-negative cohort (5 (5 %) luminal, 83(95 %) non-luminal). Recurrence-free, and overall, survival rates were similar in both groups (p = 0.4 and 0.5, respectively) despite adjuvant hormonal therapy prescribed in the majority (59 %) of weakly positive ER cases. Weak ER expression by IHC is a poor correlate of luminal subtype in invasive breast cancer. In the setting of highly sensitive and robust IHC methodology, cutoffs for ER status determination and subsequent systemic therapy should be revisited.
Discovery and verification of urinary peptides in type 2 diabetes mellitus with kidney injury.Friday, February 05, 2016
Fu G, Du Y, Chu L, Zhang M,
Experimental biology and medicine (Maywood, N.J.). 3-Feb-2016
Varying degrees of renal injury could lead to different changes in urinary protein composition. We want to find urinary candidate peptide biomarkers in type 2 diabetic patients with different extents of kidney injury. Two sets of patients were recruited. Discovery set: weak cationic-exchange magnetic beads coupled with matrix-assisted laser desorption ionization time-of-flight mass spectrometry were used to profile the low-molecular weight peptidome in urine samples from type 2 diabetes patients with normoalbuminura and microalbuminuria. The differently expressed urinary peptides were screened by ClinProTools2.1 bioinformatics software and identified through nano-liquid chromatography-tandem mass spectrometry. Verification set: the above screened urinary peptides were validated by use matrix-assisted laser desorption ionization time-of-flight mass spectrometry on another group of type 2 diabetes patients with different extents use of kidney injury. In the screening and identification stages, seven urinary peptides were selected as the most promising biomarker candidates, and they were identified as fragments of vitronectin precursor, isoform 1 of fibrinogen alpha chain precursor, prothrombin precursor and inter-alpha-trypsin inhibitor heavy chain H4. The diagnostic efficacy of these urinary peptides was evaluated by area under the receiver operating characteristic curve, and they were 0.767, 0.768, 0.868, 0.910, 0.860, 0.843, and 0.865, respectively. In the verification stage, m/z 1743.9, 2154, 2175.5, and 2184.9 were decreased as albumin-to-creatinine (Alb/Cre) increased and m/z 2231.1, 2430.8, and 2756.1 were elevated as Alb/Cre rose. These small molecule peptides are related to type 2 diabetes kidney damage, and they may play an important role in monitoring type 2 diabetes.
Source: NCBI - Disclaimer and Copyright notice
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