scholarly journals DNA Methylation at the Novel CpG Sites in the Promoter of MED15/PCQAP Gene as a Biomarker for Head and Neck Cancers

2014 ◽  
Vol 9 ◽  
pp. BMI.S16199 ◽  
Author(s):  
Dmitry A. Ovchinnikov ◽  
Yunxia Wan ◽  
William B. Coman ◽  
Pratibala Pandit ◽  
Justin J. Cooper-White ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Head And Neck ◽  
Transcription Initiation ◽  
Normal Tissue ◽  
Cpg Methylation ◽  
Head And Neck Cancers ◽  
Diagnostic Methods ◽  
Regulation Of Transcription ◽  
Healthy Controls ◽  
Non Invasive

Head and neck cancers (HNCs) represent a significant and ever-growing burden to the modern society, mainly due to the lack of early diagnostic methods. A significant number of HNCs is often associated with drinking, smoking, chewing beetle nut, and human papilloma virus (HPV) infections. We have analyzed DNA methylation patterns in tumor and normal tissue samples collected from head and neck squamous cell carcinoma (HNSCC) patients who were smokers. We have identified novel methylation sites in the promoter of the mediator complex subunit 15 ( MED15/PCQAP) gene (encoing a co-factor important for regulation of transcription initiation for promoters of many genes), hyper methylated specifically in tumor cells. Two clusters of CpG dinucleotides methylated in tumors, but not in normal tissue from the same patients, were identified. These CpG methylation events in saliva samples were further validated in a separate cohort of HNSCC patients (who developed cancer due to smoking or HPV infections) and healthy controls using methylation-specific PCR (MSP). We used saliva as a biological medium because of its non-invasive nature, close proximity to the tumors, easiness and it is an economically viable option for large-scale screening studies. The methylation levels for the two identified CpG clusters were significantly different between the saliva samples collected from healthy controls and HNSCC individuals (Welch's t-test returning P < 0.05 and Mann–Whitney test P < 0.01 for both). The developed MSP assays also provided a good discriminative ability with AUC values of 0.70 ( P < 0.01) and 0.63 ( P < 0.05). The identified novel CpG methylation sites may serve as potential non-invasive biomarkers for detecting HNSCC.

Non-invasive label-free investigation and typing of head and neck cancers by multimodal nonlinear microscopy

2012 ◽  
Author(s):  
Tobias Meyer ◽  
Nadine Vogler ◽  
Benjamin Dietzek ◽  
Denis Akimov ◽  
Johanna Inhestern ◽  
...  
Keyword(s):  
Head And Neck ◽  
Head And Neck Cancers ◽  
Nonlinear Microscopy ◽  
Label Free ◽  
Non Invasive

scholarly journals Salivary DNA methylation panel to diagnose HPV-positive and HPV-negative head and neck cancers

BMC Cancer ◽  
2016 ◽  
Vol 16 (1) ◽  
Author(s):  
Yenkai Lim ◽  
Yunxia Wan ◽  
Dimitrios Vagenas ◽  
Dmitry A. Ovchinnikov ◽  
Chris F. L. Perry ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Head And Neck ◽  
Head And Neck Cancers

scholarly journals DNA methylation markers for diagnosis and prognosis of common cancers

2017 ◽  
Vol 114 (28) ◽  
pp. 7414-7419 ◽  
Author(s):  
Xiaoke Hao ◽  
Huiyan Luo ◽  
Michal Krawczyk ◽  
Wei Wei ◽  
Wenqiu Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Cancer Biology ◽  
Normal Tissue ◽  
Diagnostic Methods ◽  
Adjacent Normal Tissue ◽  
Tissue Samples ◽  
Diagnosis And Prognosis ◽  
Cancer Metastases ◽  
Colorectal Cancer Metastases

The ability to identify a specific cancer using minimally invasive biopsy holds great promise for improving the diagnosis, treatment selection, and prediction of prognosis in cancer. Using whole-genome methylation data from The Cancer Genome Atlas (TCGA) and machine learning methods, we evaluated the utility of DNA methylation for differentiating tumor tissue and normal tissue for four common cancers (breast, colon, liver, and lung). We identified cancer markers in a training cohort of 1,619 tumor samples and 173 matched adjacent normal tissue samples. We replicated our findings in a separate TCGA cohort of 791 tumor samples and 93 matched adjacent normal tissue samples, as well as an independent Chinese cohort of 394 tumor samples and 324 matched adjacent normal tissue samples. The DNA methylation analysis could predict cancer versus normal tissue with more than 95% accuracy in these three cohorts, demonstrating accuracy comparable to typical diagnostic methods. This analysis also correctly identified 29 of 30 colorectal cancer metastases to the liver and 32 of 34 colorectal cancer metastases to the lung. We also found that methylation patterns can predict prognosis and survival. We correlated differential methylation of CpG sites predictive of cancer with expression of associated genes known to be important in cancer biology, showing decreased expression with increased methylation, as expected. We verified gene expression profiles in a mouse model of hepatocellular carcinoma. Taken together, these findings demonstrate the utility of methylation biomarkers for the molecular characterization of cancer, with implications for diagnosis and prognosis.

Lymphocyte apoptosis as a predictive biomarker for radiotherapy de-intensification in EBV-associated nasopharynx cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e17545-e17545
Author(s):  
Kevin Lee Min Chua ◽  
Waseem Ahamed Shihabuddeen ◽  
Than Than Shwe ◽  
Sze Huey Tan ◽  
Joseph Wee ◽  
...  
Keyword(s):  
Head And Neck ◽  
Immune Cells ◽  
Normal Tissue ◽  
Locally Advanced ◽  
Predictive Biomarker ◽  
Head And Neck Cancers ◽  
Phase Iii ◽  
Tumor Control ◽  
Lymphocyte Apoptosis ◽  
Nasopharynx Cancer

e17545 Background: Emerging evidence in viral-associated head and neck cancers supports the concept of dose de-intensification in these radiosensitive tumors, but different strategies exist in selecting patients for treatment de-intensification. We hypothesize that patients who develop severe late toxicities (LT) to radiation (RT) have better tumor control, due to a common radiosensitivity index. Here, we investigate the utility of a normal tissue radiosensitivity assay (RT-induced lymphocyte apoptosis, RILA) in predicting clinical outcomes (tumor control and normal tissue toxicity) of patients with EBV-associated nasopharynx cancer (NPC). Methods: RILA assay was assessed in a cohort of locally advanced NPC patients from a randomized controlled phase III trial (N = 172, NCC0901) of cisplatin-RT with or without induction gemcitabine, carboplatin and paclitaxel. LT was assessed by CTCAE v.2 at the following intervals (2 mo yr 1, 4 mo yr 2, 6 mo yr 3-5, annually thereafter). We performed the RILA assay (48 h post 8 Gy) in a subset of cases (N = 87). Results: At a median follow-up of 5.7y, DFS (3y 74.9% GCP vs 67.4% Control, p = 0.362) and incidence of severe Grade ≥3 LT did not differ between the treatment arms. In keeping with our hypothesis, onset of severe LT was associated with reduced risk of disease relapse; OR 0.19 (95% CI = 0.02 – 1.59, p = 0.168). High %RILA, stratified by top quartile, was associated with severe LT (OR 1.92 [95% CI = 0.67-5.5], p = 0.26); and lower rate of recurrence (4.5% (1/22), high %RILA vs19.7% (12/61), low %RILA, p = 0.086). Interestingly, subset analyses revealed that CD8+, but not CD4+ subpopulation of immune cells, was strongly associated with recurrence; OR 8.58 for low %CD8-RILA (p = 0.001). Conclusions: Herein, we showed that %RILA may be a useful biomarker for tumor and normal tissue radiosensitivity of EBV-associated NPC. If validated, this predictive assay will enable precision matching of RT-sensitive patients for de-intensification in EBV- and other viral-associated head and neck cancers. The association between tumor control and CD8-subset of immune cells suggests an immune dependency for RT.

High resolution mapping of nucleic acid containing complexes in vitro and in situ

1996 ◽  
Vol 54 ◽  
pp. 48-49
Author(s):  
D. P. Bazett-Jones ◽  
M. J. Hendzel
Keyword(s):  
Nucleic Acid ◽  
High Resolution ◽  
Transcription Initiation ◽  
Molecular Mechanisms ◽  
Heavy Atom ◽  
Regulation Of Transcription ◽  
High Exposure ◽  
Resolution Mapping ◽  
Tata Sequence

Structural analysis of combinations of nucleosomes and transcription factors on promoter and enhancer elements is necessary in order to understand the molecular mechanisms responsible for the regulation of transcription initiation. Such complexes are often not amenable to study by high resolution crystallographic techniques. We have been applying electron spectroscopic imaging (ESI) to specific problems in molecular biology related to transcription regulation. There are several advantages that this technique offers in studies of nucleoprotein complexes. First, an intermediate level of spatial resolution can be achieved because heavy atom contrast agents are not necessary. Second, mass and stoichiometric relationships of protein and nucleic acid can be estimated by phosphorus detection, an element in much higher proportions in nucleic acid than protein. Third, wrapping or bending of the DNA by the protein constituents can be observed by phosphorus mapping of the complexes. Even when ESI is used with high exposure of electrons to the specimen, important macromolecular information may be provided. For example, an image of the TATA binding protein (TBP) bound to DNA is shown in the Figure (top panel). It can be seen that the protein distorts the DNA away from itself and much of its mass sits off the DNA helix axis. Moreover, phosphorus and mass estimates demonstrate whether one or two TBP molecules interact with this particular promoter TATA sequence.

The Utility of Non-invasive Tests for Detection of Previous Proximal-vein Thrombosis

1995 ◽  
Vol 73 (04) ◽  
pp. 592-596 ◽  
Author(s):  
Sabina Villalta ◽  
Paolo Prandoni ◽  
Alberto Cogo ◽  
Paola Bagatella ◽  
Andrea Piccioli ◽  
...  
Keyword(s):  
Clinical Evaluation ◽  
Femoral Vein ◽  
Clinical Score ◽  
Diagnostic Methods ◽  
Popliteal Vein ◽  
Venous Reflux ◽  
Study Objective ◽  
Vein Thrombosis ◽  
Non Invasive ◽  
The Common

SummaryBackground. Despite the availability of several diagnostic methods for the detection of deep-vein thrombosis (DVT), the identification of previous episodes of DVT remains a diagnostic challenge.Study objective. To assess the reliability of a combination of a standardized clinical score with three non-invasive tests: compression ultrasonography (CUS), Doppler ultrasound (DUS), and photoplethysmography (PPG), in determining the presence or the absence of previous proximal DVT.Methods. One hundred consecutive unselected outpatients were identified, who had undergone contrast venography six to nine years previously because of the clinical suspicion of DVT (confirmed in 43). They were blindly reinvestigated by a panel of trained operators unaware of venography results. They underwent a clinical evaluation of the lower limb, by applying a standardized score to five symptoms and six signs (grading each item from 0 to 3); a PPG test to determine the venous refilling time; a DUS test to determine the venous reflux separately in the common femoral and the popliteal vein; and a CUS test to determine vein compressibility in the same regions.Results. An abnormal CUS test and/or the demonstration of venous reflux in the popliteal region and/or a high clinical score (≥ 8) identified twenty-four of the 43 (56%) DVT + patients with a specificity of 89%. The combination of normal CUS with the absence of venous reflux in both the common femoral and popliteal vein and a low clinical score excluded previous thrombosis in 45 (79%) of the 57 DVT- patients (negative predictive value, 78%). Abnormal venous reflux in the isolated common femoral vein did not reliably predict the presence or absence of previous DVT. However, this occurred in only 13 (13%) patients. The PPG determination of venous refilling time did not improve the results obtained with the other tests.Conclusions. The combination of a standardized clinical evaluation with the results of CUS and DUS can reliably diagnose or exclude previous proximal-vein thrombosis in almost 90% of patients with previous episodes of suspected DVT.

Diagnosis of helicobacter pylori infection: problems and prospects

2020 ◽  
pp. 54-59
Author(s):  
A. S. Molostova ◽  
N. S. Gladyshev ◽  
A. V. Svarval ◽  
R. S. Ferman ◽  
A. B. Karasyova ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Urease Activity ◽  
Diagnostic Methods ◽  
Study Group ◽  
Biochemical Method ◽  
Antimicrobial Drugs ◽  
Non Invasive ◽  
Number Of Patients ◽  
Pcr Method ◽  
Positive Results

(HP) infection was performed using invasive and non-invasive methods. The study group consisted of 95 patients with dyspepsia. HP infection was detected in 47 patients (49.4 %). The expediency of using a set of diagnostic methods for detecting HP (PCR, immunochromatographic, bacteriological and method for determining urease activity) is proved. Most often (100 %) in patients HP infection was detected in biopsies using the PCR method. Somewhat less frequently it was detected when examining biopsies with an invasive biochemical method (AMA RUT Reader) (82 %) and fecal immunochromatographic method (83 %). Despite the fact that helicobacteriosis was detected bacteriologically in a small number of patients (24 %), this method is of particular value, since it allows you to assess the sensitivity to antimicrobial drugs and probiotics, and does not give false positive results.

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