Objectives
MRI can detect early-stage nasopharyngeal carcinoma (NPC), but the detection is more challenging in early-stage NPCs because they must be distinguished from benign hyperplasia in the ...nasopharynx. This study aimed to determine whether intravoxel incoherent motion diffusion-weighted imaging (IVIM DWI) MRI could distinguish between these two entities.
Methods
Thirty-four subjects with early-stage NPC and 30 subjects with benign hyperplasia prospectively underwent IVIM DWI. The mean pure diffusion coefficient (
D
), pseudo-diffusion coefficient (
D
*), perfusion fraction (
f
) and apparent diffusion coefficient (ADC) values were calculated for all subjects and compared between the 2 groups using Student’s
t
test. Receiver operating characteristics with the area under the curve (AUC) was used to identify the optimal threshold for all significant parameters, and the corresponding diagnostic performance was calculated. A
p
value of < 0.05 was considered statistically significant.
Results
Compared with benign hyperplasia, early-stage NPC exhibited a significantly lower
D
mean (0.64 ± 0.06 vs 0.87 ± 0.11 × 10
−3
mm
2
/s), ADC
0–1000
mean (0.77 ± 0.08 vs 1.00 ± 0.13 × 10
−3
mm
2
/s), ADC
300–1000
(0.63 ± 0.05 vs 0.86 ± 0.10 × 10
−3
mm
2
/s) and a higher
D
* mean (32.66 ± 4.79 vs 21.96 ± 5.21 × 10
−3
mm
2
/s) (all
p
< 0.001). No significant difference in the
f
mean was observed between the two groups (
p
= 0.216). The
D
and ADC
300–1000
mean had the highest AUC of 0.985 and 0.988, respectively, and the D mean of < 0.75 × 10
−3
mm
2
/s yielded the highest sensitivity, specificity and accuracy (100%, 93.3% and 96.9%, respectively) in distinguishing early-stage NPC from benign hyperplasia.
Conclusion
DWI has potential to distinguish early-stage NPC from benign hyperplasia and
D
and ADC
300–1000
mean were the most promising parameters.
Key Points
• Diffusion-weighted imaging has potential to distinguish early-stage nasopharyngeal carcinoma from benign hyperplasia in the nasopharynx.
• The pure diffusion coefficient, pseudo-diffusion coefficient from intravoxel incoherent motion model and apparent diffusion coefficient from conventional diffusion-weighted imaging were significant parameters for distinguishing these two entities in the nasopharynx.
• The pure diffusion coefficient, followed by apparent diffusion coefficient, may be the most promising parameters to be used in screening studies to help detect early-stage nasopharyngeal carcinoma.
Abstract
Introduction: Breast cancer is the most common malignancy and 3rd leading cause of deaths among the female population in Hong Kong. Since the establishment of The Hong Kong Hereditary Breast ...Cancer Family Registry in 2007, 1344 patients with breast and/or ovarian cancer who met the selection criteria were recruited for genetic testing in Hong Kong. Since 2011 we started to employ next-generation DNA sequencing (NGS) to expedite the analysis workflow and expand the panel of genes for sequencing.
Aim: To evaluate the workflow of NGS in mutation screening of BRCA1, BRCA2, TP53 and PTEN genes, and compared with the sequence data obtained by Sanger sequencing.
Methods: We sequenced BRCA1, BRCA2, TP53 and PTEN genes in peripheral blood samples of 410 patients, 53 positive controls and 107 healthy local individuals using 454 GS Junior System. Generation of barcoded amplicon libraries was streamlined by microfluidic PCR using Fluidigm Access Array System. Sequencing data were analyzed by an in-house developed fully automatic bioinformatics pipeline, which mainly consists of GS Amplicon Variant Analyzer, SAMtools and Ensembl Variant Effect Predictor. All putative mutations identified were validated by Sanger sequencing. Furthermore, the frequency of BRCA1, BRCA2 and PTEN missense variants of unknown significance (VUS) identified in the cohort were compared among 107 healthy local individuals and 1000 Genomes project samples. The VUS were also subjected to a panel of in silico prediction methods including PolyPhen and SIFT.
Results: Among 410 patients, there were 7 in BRCA1, 6 in BRCA2 and 1 in TP53 mutations found, including 1 novel recurrent BRCA2 (c.7007G>T) and 1 novel founder BRCA2 (c.5164_5165delAG) mutations. Based on multiple criteria, 12 in BRCA1, 12 in BRCA2 and 1 in PTEN VUS could be prioritized for further investigation. The bioinformatics pipeline was extensively evaluated with Sanger-validated controls. The evaluation determined minimum sequencing coverage needed in this sequencing platform for accurate analysis. The pipeline accuracy was demonstrated by successful detecting mutations from 53 positive controls, including single nucleotide variants, insertions and deletions in different sequence context.
Conclusion: BRCA1, BRCA2, TP53 and PTEN mutation screening of 410 patients were expedited by high-throughput DNA sequencing. This method could detect 14 positive cases, including recurrent mutations, in a shorter period of time when compared with Sanger full gene sequencing. High-risk patients who are negative for the gene panel may need further investigation other than screening for BRCA1/2. The in-house developed bioinformatics pipeline was validated to detect various types of mutations and potentially become a conventional platform for genetic screening.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-07-03.
Neovascularization of the adventitial vasa vasorum with extension into the intima of atherosclerotic lesions is frequently observed, but its pathophysiological significance is still subject to ...debate. Recently, leptin, the product of the Ob gene, was identified. Leptin, via activation of the endothelial receptor (Ob-R), generates a growth signal involving a tyrosine kinase-dependent intracellular pathway and promotes angiogenic processes. We hypothesized that a high concentration of leptin within vasa vasorum and plaque itself, may influence inflammatory and vascular neovascularization coupling with functional upregulation of the vascular endothelial growth factor (VEGF). Microscopic computerized tomography was utilized for the spatial distribution of vasa vasorum and intimal neovascularization from atherosclerotic human coronary arteries. Atherosclerotic coronary arteries showed a dense plexus of microvessels in the adventitia and plaque itself. Microscopic analysis from human atherosclerotic aortas revealed an increase in the intimal thickness with neovascularization. The immunoreactivity for Ob-R, VEGF and matrix metalloproteinase (MMP) increased in atherosclerotic plaque, predominantly in the endothelial lining of the intimal neovessel and macrophages/foam cells. Our observation of a prominent colocalization between Ob-R, VEGF and MMP supports this hypothesis and these factors participate in the neovascularization of atherosclerotic lesions. The present study is the first report on vascular tissue and it opens a promising perspective concerning future investigations of leptin-dependent modulation of atherogenesis and vascular neovascularization under pathophysiolgical conditions.
Background Ongoing evaluation of biological agents in patients with moderate-to-severe psoriasis is needed to support their long-term use. Objective To evaluate long-term efficacy and safety of ...ustekinumab through 5years in the PHOENIX 1 study. Methods Patients were randomized to placebo or ustekinumab (45mg or 90mg) at Weeks 0, 4 and every-12-weeks thereafter; placebo patients crossed-over to ustekinumab at Week 12. Clinical response through Week 244 was evaluated using the Psoriasis Area and Severity Index (PASI) in the Overall Population (i.e. patients receiving greater than or equal to 1 dose of ustekinumab), Initial Responders (i.e. PASI 75 responders Weeks 28/40 re-randomized at Week 40 to continue every-12-week maintenance) and Partial Responders (i.e. <PASI 75 responders adjusted to every-8-week maintenance at Weeks 28 or 40). Safety endpoints were evaluated through Week 264 for the Overall Population. Results Overall, 68.7% (517/753) of ustekinumab-treated patients completed treatment through Week 244. Initial clinical responses were generally maintained through Week 244 (PASI 75: 63.4% and 72.0%; PASI 90: 39.7% and 49.0%; PASI 100: 21.6% and 26.4%) for patients receiving 45mg and 90mg, respectively. Similarly, PASI 75 responses were generally maintained among Initial Responders 79.1% (45mg) and 80.8%(90mg) and Partial Responders 57.6% (45mg) and 55.1%(90mg). With 3104 patient-years of follow-up, rates of overall adverse events (AEs), serious AEs, serious infections, malignancies and major adverse cardiovascular events were generally consistent over time and comparable between doses. Conclusions Through 5years of continuous treatment, ustekinumab demonstrated stable clinical response and a safety profile consistent with previous reports.
A sensitive search for the rare decays {Omega}{sup -} {yields} {Lambda}{pi}{sup -} and {Xi}{sup 0} {yields} p{pi}{sup -} has been performed using data from the 1997 run of the HyperCP (Fermilab E871) ...experiment. Limits on other such processes do not exclude the possibility of observable rates for |{Delta}S| = 2 nonleptonic hyperon decays, provided the decays occur through parity-odd operators. They obtain the branching-fraction limits {Beta}({Omega}{sup -} {yields} {Lambda}{pi}{sup -}) < 2.9 x 10{sup -6} and {Beta}({Xi}{sup 0} {yields} p{pi}{sup -}) < 8.2 x 10{sup -6}, both at 90% confidence level.
Massively parallel sequencing of DNA molecules in the plasma of pregnant women has been shown to allow accurate and noninvasive prenatal detection of fetal trisomy 21. However, whether the sequencing ...approach is as accurate for the noninvasive prenatal diagnosis of trisomy 13 and 18 is unclear due to the lack of data from a large sample set. We studied 392 pregnancies, among which 25 involved a trisomy 13 fetus and 37 involved a trisomy 18 fetus, by massively parallel sequencing. By using our previously reported standard z-score approach, we demonstrated that this approach could identify 36.0% and 73.0% of trisomy 13 and 18 at specificities of 92.4% and 97.2%, respectively. We aimed to improve the detection of trisomy 13 and 18 by using a non-repeat-masked reference human genome instead of a repeat-masked one to increase the number of aligned sequence reads for each sample. We then applied a bioinformatics approach to correct GC content bias in the sequencing data. With these measures, we detected all (25 out of 25) trisomy 13 fetuses at a specificity of 98.9% (261 out of 264 non-trisomy 13 cases), and 91.9% (34 out of 37) of the trisomy 18 fetuses at 98.0% specificity (247 out of 252 non-trisomy 18 cases). These data indicate that with appropriate bioinformatics analysis, noninvasive prenatal diagnosis of trisomy 13 and trisomy 18 by maternal plasma DNA sequencing is achievable.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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