PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-6 (6)
 

Clipboard (0)
None
Journals
Year of Publication
Document Types
1.  Differential radio-sensitivities of human chromosomes 1 and 2 in one donor in interphase- and metaphase-spreads after 60Co γ-irradiation 
Background
Radiation-induced chromosome aberrations lead to a plethora of detrimental effects at cellular level. Chromosome aberrations provide broad spectrum of information ranging from probability of malignant transformation to assessment of absorbed dose. Studies mapping differences in radiation sensitivities between human chromosomes are seldom undertaken. Consequently, health risk assessment based on radio-sensitivities of individual chromosomes may be erroneous. Our efforts in this article, attempt to demonstrate differences in radio-sensitivities of human chromosome-1 and/or -2, both in interphase and metaphase spreads.
Methods
Upon blood collection, dosimetry and irradiation were performed. Lymphocytes were isolated after whole-blood irradiation with 60Co γ-rays in the dose range of 0–5 Gy for both interphase, and metaphase aberration studies. Induction of premature chromosome condensation in interphase cells was accomplished using a phosphatase inhibitor, calyculin-A. Metaphase spreads were harvested from short-term peripheral blood lymphocyte cultures following colcemid arrest and using an automated metaphase harvester and spreader. Aberration analysis in both interphase and metaphase spreads were done using FISH.
Results
In interphase, aberrant cell and aberration frequency involving chromosome 1 and/or 2 increased linearly with radiation dose. In metaphase, aberrations increased in a linear-quadratic manner with dose. Our studies ascertain that chromosome-2 is more radio-sensitive than chromosome-1 in both interphase and metaphase stages, albeit the DNA content of chromosome-2 is lesser than chromosome-1 by almost 10 million base pairs.
Conclusion
Differences in radio-sensitivities of chromosomes have implications in genetic damage, chromosome organization, and chromosome function. Designing research experiments based on our vital findings may bring benefit to radiation-induced risk assessment, therapeutics and development of chromosome specific biomarkers.
doi:10.1186/1756-6649-9-6
PMCID: PMC2704179  PMID: 19531236
2.  Prognostic implication of late gadolinium enhancement on cardiac MRI in light chain (AL) amyloidosis on long term follow up 
Background
Light chain amyloidosis (AL) is a rare plasma cell dyscrasia associated with poor survival especially in the setting of heart failure. Late gadolinium enhancement (LGE) on cardiac MRI was recently found to correlate with myocardial amyloid deposition but the prognostic role is not established. The aim is to determine the prognostic significance of LGE in AL by comparing long term survival of AL patients with and without LGE.
Methods
Twenty nine consecutive patients (14 females; 62 ± 11 years) with biopsy-proven AL undergoing cardiac MRI with gadolinium as part of AL workup were included. Survival was prospectively followed 29 months (median) following MRI and compared between those with and without LGE by Kaplan-Meier and log-rank analyses.
Results
LGE was positive in 23 subjects (79%) and negative in 6 (21%). Left ventricular ejection fraction was 66 ± 17% in LGE-positive and 69 ± 12% in LGE-negative patients (p = 0.8). Overall 1-year mortality was 36%. On follow-up, 14/23 LGE-positive and none of LGE-negative patients died (log rank p = 0.0061). Presenting New York Heart Association heart failure class was also associated with poor survival (p = 0.0059). Survival between two LGE groups stratified by heart failure class still showed a significant difference by a stratified log-rank test (p = 0.04).
Conclusion
Late gadolinium enhancement is common and is associated with poor long-term survival in light chain amyloidosis, even after adjustment for heart failure class presentation. The prognostic significance of late gadolinium enhancement in this disease may be useful in patient risk-stratification.
doi:10.1186/1756-6649-9-5
PMCID: PMC2686669  PMID: 19416541
3.  Average arterial input function for quantitative dynamic contrast enhanced magnetic resonance imaging of neck nodal metastases 
Background
The present study determines the feasibility of generating an average arterial input function (Avg-AIF) from a limited population of patients with neck nodal metastases to be used for pharmacokinetic modeling of dynamic contrast-enhanced MRI (DCE-MRI) data in clinical trials of larger populations.
Methods
Twenty patients (mean age 50 years [range 27–77 years]) with neck nodal metastases underwent pretreatment DCE-MRI studies with a temporal resolution of 3.75 to 7.5 sec on a 1.5T clinical MRI scanner. Eleven individual AIFs (Ind-AIFs) met the criteria of expected enhancement pattern and were used to generate Avg-AIF. Tofts model was used to calculate pharmacokinetic DCE-MRI parameters. Bland-Altman plots and paired Student t-tests were used to describe significant differences between the pharmacokinetic parameters obtained from individual and average AIFs.
Results
Ind-AIFs obtained from eleven patients were used to calculate the Avg-AIF. No overall significant difference (bias) was observed for the transfer constant (Ktrans) measured with Ind-AIFs compared to Avg-AIF (p = 0.20 for region-of-interest (ROI) analysis and p = 0.18 for histogram median analysis). Similarly, no overall significant difference was observed for interstitial fluid space volume fraction (ve) measured with Ind-AIFs compared to Avg-AIF (p = 0.48 for ROI analysis and p = 0.93 for histogram median analysis). However, the Bland-Altman plot suggests that as Ktrans increases, the Ind-AIF estimates tend to become proportionally higher than the Avg-AIF estimates.
Conclusion
We found no statistically significant overall bias in Ktrans or ve estimates derived from Avg-AIF, generated from a limited population, as compared with Ind-AIFs.
However, further study is needed to determine whether calibration is needed across the range of Ktrans. The Avg-AIF obtained from a limited population may be used for pharmacokinetic modeling of DCE-MRI data in larger population studies with neck nodal metastases. Further validation of the Avg-AIF approach with a larger population and in multiple regions is desirable.
doi:10.1186/1756-6649-9-4
PMCID: PMC2679707  PMID: 19351382
4.  Bone turnover markers are correlated with total skeletal uptake of 99mTc-methylene diphosphonate (99mTc-MDP) 
Background
Skeletal uptake of 99mTc labelled methylene diphosphonate (99mTc-MDP) is used for producing images of pathological bone uptake due to its incorporation to the sites of active bone turnover. This study was done to validate bone turnover markers using total skeletal uptake (TSU) of 99mTc-MDP.
Methods
22 postmenopausal women (52–80 years) volunteered to participate. Scintigraphy was performed by injecting 520 MBq of 99mTc-MDP and taking whole body images after 3 minutes, and 5 hours. TSU was calculated from these two images by taking into account the urinary loss and soft tissue uptake. Bone turnover markers used were bone specific alkaline phosphatase (S-Bone ALP), three different assays for serum osteocalcin (OC), tartrate resistant acid phosphatase 5b (S-TRACP5b), serum C-terminal cross-linked telopeptides of type I collagen (S-CTX-I) and three assays for urinary osteocalcin (U-OC).
Results
The median TSU of 99mTc-MDP was 23% of the administered activity. All bone turnover markers were significantly correlated with TSU with r-values from 0.52 (p = 0.013) to 0.90 (p < 0.001). The two resorption markers had numerically higher correlations (S-TRACP5b r = 0.90, S-CTX-I r = 0.80) than the formation markers (S-Total OC r = 0.72, S-Bone ALP r = 0.66), but the difference was not statistically significant. TSU did not correlate with age, weight, body mass index or bone mineral density.
Conclusion
In conclusion, bone turnover markers are strongly correlated with total skeletal uptake of 99mTc-MDP. There were no significant differences in correlations for bone formation and resorption markers. This should be due to the coupling between formation and resorption.
doi:10.1186/1756-6649-9-3
PMCID: PMC2674029  PMID: 19331678
5.  Repeatability of regional myocardial blood flow calculation in 82Rb PET imaging 
Background
We evaluated the repeatability of the calculation of myocardial blood flow (MBF) at rest and pharmacological stress, and calculated the coronary flow reserve (CFR) utilizing 82Rb PET imaging. The aim of the research was to prove high repeatability for global MBF and CFR values and good repeatability for regional MBF and CFR values. The results will have significant impact on cardiac PET imaging in terms of making it more affordable and increasing its use.
Methods
12 normal volunteers were imaged at rest and during pharmacological stress, with 2220 MBq of 82Rb each. A GE Advance PET system was used to acquire dynamic 50-frame studies. MBF was calculated with a 2-compartmental model using a modified PMOD program (PMOD; University Hospital Zurich, Zurich, Switzerland). Two differential equations, describing a 2-compartmental model, were solved by numerical integration and using Levenberg-Marquardt's method for fitting data. The PMOD program defines 16 standard segments and calculates myocardial flow for each segment, as well as average septal, anterior, lateral, inferior and global flow. Repeatability was evaluated according to the method of Bland and Altman.
Results
Global rest and stress MBF, as well as global CFR, showed very good repeatability. No significant differences were found between the paired resting global MBF (0.63 ± 0.13 vs. 0.64 ± 0.13 mL/min/g; mean difference, -1.0% ± 2.6%) and the stress global MBF (1.37 ± 0.23 vs. 1.37 ± 0.24; mean difference, 0.1% ± 2.3%). Global CFR was highly reproducible (2.25 ± 0.56 vs. 2.22 ± 0.54, P = not statistically significant; mean difference, 1.3% ± 14.3%). Repeatability coefficients for global rest MBF were 0.033 (5.2%) and stress MBF 0.062 (4.5%) mL/min/g. Regional rest and stress MBF and CFR have shown good reproducibility. The average per sector repeatability coefficients for rest MBF were 0.056 (8.5%) and stress MBF 0.089 (6.3%) mL/min/g, and average repeatability coefficient for CFR was 0.25 (10.6%).
Conclusion
The results of the study show that software calculation of MBF and CFR with 82Rb myocardial PET imaging is highly repeatable for global values and has good repeatability for regional values.
doi:10.1186/1756-6649-9-2
PMCID: PMC2646684  PMID: 19178700
6.  Chemotherapeutic treatment efficacy and sensitivity are increased by adjuvant alternating electric fields (TTFields) 
Background
The present study explores the efficacy and toxicity of combining a new, non-toxic, cancer treatment modality, termed Tumor Treating Fields (TTFields), with chemotherapeutic treatment in-vitro, in-vivo and in a pilot clinical trial.
Methods
Cell proliferation in culture was studied in human breast carcinoma (MDA-MB-231) and human glioma (U-118) cell lines, exposed to TTFields, paclitaxel, doxorubicin, cyclophosphamide and dacarbazine (DTIC) separately and in combinations. In addition, we studied the effects of combining chemotherapy with TTFields in an animal tumor model and in a pilot clinical trial in recurrent and newly diagnosed GBM patients.
Results
The efficacy of TTFields-chemotherapy combination in-vitro was found to be additive with a tendency towards synergism for all drugs and cell lines tested (combination index ≤ 1). The sensitivity to chemotherapeutic treatment was increased by 1–3 orders of magnitude by adjuvant TTFields therapy (dose reduction indexes 23 – 1316). Similar findings were seen in an animal tumor model. Finally, 20 GBM patients were treated with TTFields for a median duration of 1 year. No TTFields related systemic toxicity was observed in any of these patients, nor was an increase in Temozolomide toxicity seen in patients receiving combined treatment. In newly diagnosed GBM patients, combining TTFields with Temozolomide treatment led to a progression free survival of 155 weeks and overall survival of 39+ months.
Conclusion
These results indicate that combining chemotherapeutic cancer treatment with TTFields may increase chemotherapeutic efficacy and sensitivity without increasing treatment related toxicity.
doi:10.1186/1756-6649-9-1
PMCID: PMC2647898  PMID: 19133110

Results 1-6 (6)