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  • 1
    Keywords: CANCER ; tumor ; carcinoma ; Germany ; LUNG ; PERFUSION ; THERAPY ; CT ; DENSITY ; LUNG-CANCER ; NEW-YORK ; TUMORS ; PATIENT ; CONTRAST ; INJECTION ; treatment ; DIFFERENCE ; REGION ; REGIONS ; LOCALIZATION ; PARAMETERS ; tomography ; CARCINOMAS ; COMPUTED-TOMOGRAPHY ; PET ; lung neoplasms ; PULMONARY ; DYNAMIC CT ; X-ray computed
    Abstract: Advanced bronchial carcinomas by means of perfusion and peak enhancement using dynamic contrast-enhanced multislice CT are characterized. Twenty-four patients with advanced bronchial carcinoma were examined. During breathhold, after injection of a contrast-medium (CM), 25 scans were performed (I scan/s) at a fixed table position. Density-time curves were evaluated from regions of interest of the whole tumor and high- and low-enhancing tumor areas. Perfusion and peak enhancement were calculated using the maximum-slope method of Miles and compared with size, localization (central or peripheral) and histology. Perfusion of large tumors (〉50 cm(3)) averaged over both the whole tumor (P=0.001) and the highest enhancing area (P=0.003) was significantly lower than that of smaller ones. Independent of size, central carcinomas had a significantly (P=0.04) lower perfusion (mean 27.9 ml/min/100 g) than peripheral ones (mean 66.5 ml/min/100 9). In contrast, peak enhancement of central and peripheral carcinomas was not significantly different. Between non-small-cell lung cancers and small-cell lung cancers, no significant differences were observed in both parameters. In seven tumors, density increase after CM administration started earlier than in the aorta, indicating considerable blood supply from pulmonary vessels. Tumor perfusion was dependent on tumor size and localization, but not on histology. Furthermore, perfusion CT disclosed blood supply from both pulmonary and/or bronchial vessels in some tumors
    Type of Publication: Journal article published
    PubMed ID: 15029450
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  • 2
    Keywords: CANCER ; EXPRESSION ; SURVIVAL ; CELL ; COMBINATION ; Germany ; LUNG ; LUNG-CANCER ; RISK ; GENE ; GENES ; DRUG ; PATIENT ; MESSENGER-RNA ; IMPACT ; prognosis ; RISK-FACTORS ; CYCLE ; polymorphism ; POLYMORPHISMS ; single nucleotide polymorphism ; FREQUENCIES ; MEMBRANE ; SNP ; chemotherapy ; LOCALIZATION ; pharmacokinetic ; PHARMACOKINETICS ; CISPLATIN ; lung neoplasms ; PHASE-II ; SINGLE ; REGRESSION ; SINGLE NUCLEOTIDE POLYMORPHISMS ; PHARMACOGENETICS ; GENOTYPE ; RISK-FACTOR ; PROGRESSION-FREE SURVIVAL ; ABCG2 ; ABCC3 ; CONCENTRATIVE NUCLEOSIDE TRANSPORTER ; PLATINUM-BASED CHEMOTHERAPY ; CELL-LUNG-CANCER ; predictive factor ; CNT1 ; multidrug resistance-associated proteins ; RESISTANCE-ASSOCIATED PROTEIN-3 ; SCLC
    Abstract: The prognosis of lung cancer patients treated with chemotherapy is poor, motivating the search for predictive factors. Single nucleotide polymorphisms (SNPs) in membrane transporter genes could influence the pharmacokinetics of cytostatic drugs and therefore affect treatment outcome. We examined 6 SNPs with known or suspected phenotypic effect: ABCG2 G34A, C421A; ABCC3 C-211T, G3890A, C3942T and CNT1 G565A. For 349 Caucasian patients with primary lung cancer [161 small cell lung cancer (SCLC), 187 nonsmall cell lung cancer (NSCLC) and 1 mixed] receiving first-line chemotherapy 3 different endpoints were analyzed: response after the 2nd cycle (R), progression-free survival (PFS) and overall survival (OS). The prognostic value of the SNPs was analyzed using multivariable logistic regression, calculating odds ratios (ORs) when comparing genotype frequencies in responders and nonresponders after the 2nd cycle. Hazard ratios (HRs) for PFS and for OS were calculated using Cox regression methods. In all lung cancer patients, none of the investigated polymorphisms modified response statistically significant. The only significant result in the histological subpopulations was in SCLC patients carrying the ABCC3 -211T allele who showed significantly worsened PFS (HR: 1.79; 95% confidence interval (CI) 1.13-2.82). In an exploratory subgroup analysis significantly worse OS was seen for carriers of the ABCG2 421A-allele treated with platinum-based drugs (HR: 1.60; 95% CI 1.04-2.47; n = 256). In conclusion, this study prioritizes ABCC3 C-211T and ABCG2 C421A as candidate transporter SNPs to be further investigated as possible predictors of the clinical outcome of chemotherapy in lung cancer patients. (C) 2008 Wiley-Liss, Inc
    Type of Publication: Journal article published
    PubMed ID: 19107936
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  • 3
    Keywords: EXPRESSION ; INHIBITOR ; SURVIVAL ; carcinoma ; Germany ; DISEASE ; RISK ; PROTEIN ; LINES ; DNA ; MARKER ; polymorphism ; resistance ; PROMOTER ; Bcl-2 ; SOLID TUMORS ; ABT-737 ; Small cell
    Abstract: INTRODUCTION: We investigated the single-nucleotide polymorphism C-938A in the apoptotic gene BCL-2 to assess the potential impact as a genetic marker for response to chemotherapy and outcome prediction in small cell lung cancer (SCLC) patients. Such a marker might help optimize lung cancer treatment in a tailored approach. METHODS: DNA derived from peripheral blood lymphocytes of 188 Caucasian SCLC patients treated at the Thoraxklinik Heidelberg was genotyped. Chemotherapy response, time to progression (TTP), and overall survival (OS) were evaluated using multivariable regression (unconditional logistic for response and Cox proportional hazard for TTP and OS) with odds ratios and hazard ratios (HRs) and their 95% confidence intervals (CIs) as quantitative outcome measures, respectively. RESULTS: Small cell lung cancer patients carrying the BCL-2 -938CC genotype showed significantly worse TTP than patients carrying the BCL-2 -938AA genotype (HR = 1.86; 95% CI = 1.10-3.13, p = 0.021). The same adverse effect was shown for OS (HR = 2.38; 95% CI = 1.38-4.12, p = 0.002). Also, patients with limited disease (HR = 2.57; 95% CI = 1.18-5.60, p = 0.017) showed worse OS with the BCL-2 -938CC genotype. CONCLUSION: BCL-2 -938CC genotype shows significantly worse outcome in small cell lung cancer patients. This genetic marker might particularly impact on treatment strategies using BCL-2 antisense approaches.
    Type of Publication: Journal article published
    PubMed ID: 21107291
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  • 4
    Keywords: Germany ; LUNG ; PERFUSION ; THERAPY ; CT ; imaging ; PATIENT ; MRI ; SEQUENCE ; MAGNETIC-RESONANCE ; magnetic resonance imaging ; AGE ; STATISTICAL-ANALYSIS ; MORPHOLOGY ; PULMONARY PERFUSION ; BODY ; CHILDREN ; SEGMENTS ; FEASIBILITY ; BREATH-HOLD ; LUNG PERFUSION ; fibrosis ; WEIGHT ; IMPAIRMENT ; CYSTIC-FIBROSIS ; cystic fibrosis ; SMALL AIRWAYS ; DEFECT ; GRAPPA ; CIRCULATION ; lung morphology
    Abstract: This paper is a feasibility study of magnetic resonance imaging (MRI) of lung perfusion in children with cystic fibrosis (CF) using contrast-enhanced 3D MRI. Correlation assessment of perfusion changes with structural abnormalities. Eleven CF patients (9 f, 2 m; median age 16 years) were examined at 1.5 T. Morphology: HASTE coronal, transversal (TR/TE/alpha/ST: 600 ms/28 ms/180 degrees/6 mm), breath-hold 18 s. Perfusion: Time-resolved 3D GRE pulse sequence (FLASH, TE/TR/alpha: 0.8/1.9 ms/40 degrees), parallel imaging (GRAPPA, PAT 2). Twenty-five data sets were acquired after intravenous injection of 0.1 mmol/kg body weight of gadodiamide, 3-5 ml/s. A total of 198 lung segments were analyzed by two radiologists in consensus and scored for morphological and perfusion changes. Statistical analysis was performed by Mantel-Haenszel chi-square test. Results showed that perfusion defects were observed in all patients and present in 80% of upper, and 39% of lower lobes. Normal lung parenchyma showed homogeneous perfusion (86%, P 〈 0.0001). Severe morphological changes led to perfusion defects (97%, P 〈 0.0001). Segments with moderate morphological changes showed normal (53%) or impaired perfusion (47%). In conclusion, pulmonary perfusion is easy to judge in segments with normal parenchyma or severe changes. In moderately damaged segments, MRI of lung perfusion may help to better assess actual functional impairment. Contrast-enhanced 3D MRI of lung perfusion has the potential for early vascular functional assessment and therapy control in CF patients
    Type of Publication: Journal article published
    PubMed ID: 16673092
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  • 5
    Keywords: CANCER ; AGENTS ; BLOOD ; LUNG ; PERFUSION ; imaging ; lung cancer ; LUNG-CANCER ; QUANTIFICATION ; VOLUME ; DISEASE ; DISEASES ; ACCURACY ; RESOLUTION ; TIME ; PATIENT ; BLOOD-FLOW ; CONTRAST ; blood flow ; CONTRAST AGENT ; FLOW ; MR ; MRI ; SEQUENCE ; MAGNETIC-RESONANCE ; magnetic resonance imaging ; AGE ; RADIOFREQUENCY ABLATION ; PARAMETERS ; SCINTIGRAPHY ; CONTRAST AGENTS ; ANGIOGRAPHY ; CONTRAST-ENHANCED MRI ; magnetic resonance imaging (MRI) ; BODY ; PREVALENCE ; LUNG PERFUSION ; QUANTITATIVE ASSESSMENT ; MATRIX ; fibrosis ; WEIGHT ; CYSTIC-FIBROSIS ; single-lung transplantation ; functional imaging ; RETROSPECTIVE ANALYSIS ; cystic fibrosis ; VIEW ; SCANS ; RADIONUCLIDE ; perfusion scintigraphy ; ATRIAL-FIBRILLATION ; LUNG-DISEASES ; VEIN STENOSIS
    Abstract: Objectives: We sought to assess the agreement between lung perfusion ratios calculated from pulmonary perfusion magnetic resonance imaging (MRI) and those calculated from radionuclide (RN) perfasion scintigraphy. Materials and Methods: A retrospective analysis of MR and RN perfusion scans was conducted in 23 patients (mean age, 60 +/- 14 years) with different lung diseases (lung cancer 15, chronic obstructive pulmonary disease = 4, cystic fibrosis 2, and mesothelioma = 2). Pulmonary perfusion was assessed by a time-resolved contrast-enhanced 3D gradient-echo pulse sequence using parallel imaging and view sharing (TR = 1.9 milliseconds; TE = 0.8 milliseconds; parallel imaging acceleration factor = 2; partition thickness = 4 mm; matrix = 256 X 96; in-plane spatial resolution = 1.87 x 3.75 mm; scan time for each 3D dataset = 1.5 seconds), using gadolinium-based contrast agents (injection flow rate = 5 mL/s, dose = 0.1 mmol/kg of body weight). The peak concentration (PC) of the contrast agent bolus, the pulmonary blood flow (PBF), and blood volume (PBV) were computed from the signal-time curves of the lung. Left-to-right ratios of pulmonary perfasion were calculated from the MR parameters and RN counts. The agreement between these ratios was assessed for side prevalence (sign test) and quantitatively (Deming-regression). Results: MR and RN ratios agreed on side prevalence in 21 patients (91%) with PC, in 20 (87%) with PBF, and in 17 (74%) with PBV. The MR estimations of left-to-right perfusion ratios correlated significantly with those of RN perfusion scans (P 〈 0.01). The correlation was higher using PC (r = 0.67) and PBF (r = 0.66) than using PBV (r = 0.50). The MR ratios computed from PBF showed the highest accuracy, followed by those from PC and PBV. Independently from the MR parameter used, in some patients the quantitative difference between the MR and RN ratios was not negligible. Conclusions: Pulmonary perfusion MRI can be used to assess the differential blood flow of the lung. Further studies in a larger group of patients are required to fully confirm the clinical suitability of this imaging method
    Type of Publication: Journal article published
    PubMed ID: 16829745
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  • 6
    Keywords: Germany ; LUNG ; PERFUSION ; THERAPY ; FOLLOW-UP ; imaging ; VOLUME ; DISEASE ; PATIENT ; MRI ; CYCLE ; magnetic resonance imaging ; MOBILITY ; chemotherapy ; FUNCTION TESTS ; MOTION ; PLEURAL MESOTHELIOMA ; dynamic MRI ; 2D ; breathing cycle ; DIAPHRAGM ; HEALTHY-SUBJECTS ; SPIROMETRY ; volumetry ; LUNG-VOLUME ; therapy monitoring ; 3D volumetry
    Abstract: Purpose: To monitor lung motion in patients with malignant pleural mesothelioma (MPM) before and after chemotherapy (CHT) using 2-dimensional (2D) and 3-dimensional (3D) dynamic MRI (dMRI) in comparison with spirometry. Methods and Materials: Twenty-two patients with MPM were examined before CHT, as well as after 3 and 6 CHT cycles (3 months and 6 months) using 2D dMRI (trueFISP; 3 images/s) and 3D dMRI (FLASH 3D, I slab (52 slices)/s) using parallel imaging in combination with view-sharing technique. Maximum craniocaudal lung dimensions (2D) and lung volumes (3D) were monitored, separated into the tumor-bearing and nontumor-bearing hemithorax. Vital capacity (VC) was measured for comparison using spirometry. Results: Using 2D technique, there was a significant difference between the tumor-bearing and the nontumor-bearing hemithorax before CHT (P 〈 0.01) and after 3 CHT cycles (P 〈 0.05), whereas difference was not significant in the second control. In the tumor-bearing hemithorax, mobility increased significantly from the status before versus after 3 CHT cycles (4.1 +/- 1.1 cm vs. 4.8 +/- 1.4 cm, P 〈 0.05). Using 3D technique, at maximum inspiration, the volume of the tumor-bearing hemithorax was 0.6 +/- 0.4 L and of the nontumor-bearing hemithorax 1.25 +/- 0.4 L before CHT. In the follow-up exams, these volumes changed to 1.05 +/- 0.4 L (P 〈 0.05) and 1.4 +/- 0.5 L, respectively. Using spirometry, there was no significant change in VC (1.9 +/- 0.4 L vs. 2.2 +/- 0.7 L vs. 2.2 +/- 0.9 L). Conclusion: dMRI is capable of monitoring changes in lung, motion and volumetry in patients with MPM not detected by global spirornetry. Thus, dMRI is proposed for use as a further measure of therapy response
    Type of Publication: Journal article published
    PubMed ID: 16625107
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  • 7
    Keywords: APOPTOSIS ; CANCER ; EXPRESSION ; SURVIVAL ; carcinoma ; Germany ; LUNG ; PATHWAY ; lung cancer ; LUNG-CANCER ; SYSTEM ; DISEASE ; POPULATION ; RISK ; GENE ; GENES ; prognosis ; RISK-FACTORS ; CYCLE ; polymorphism ; POLYMORPHISMS ; single nucleotide polymorphism ; PROGRESSION ; risk factors ; chemotherapy ; RISK FACTOR ; CANCER-PATIENTS ; VARIANT ; PHARMACOGENETICS ; SUBGROUPS ; matrix metalloproteinase ; gelatinase B ; outcome ; single nucleotide ; journals ; ALLELE-SPECIFIC REGULATION ; ARTERY LUMINAL DIMENSIONS ; lung cancer chemotherapy ; MATRIX-METALLOPROTEINASE-3 ; STROMELYSIN
    Abstract: The prognosis for lung cancer patients treated with chemotherapy is poor. Single nucleotide polymorphisms (SNPS) in matrix metalloproteinase (MMP) genes could influence treatment outcome by altering apoptotic pathways. Eight SNPs with known or suspected phenotypic effect in six genes (MMP1, MMP2, MMP3, MMP7, MMP9 and MMP12) were investigated. For 349 Caucasian patients with primary lung cancer, receiving first-line chemotherapy, three different endpoints were analysed: response after the second cycle, progression free survival (PFS) and overall survival (OS). The prognostic value of the SNPs was analysed using multiple logistic regression for all patients and histology-, stage- and treatment-specific subgroups. Hazard ratio estimates for PFS and OS were calculated using Cox regression methods. None of the investigated polymorphisms modified response significantly in the whole patient population. However, tumour stage IIIB variant allele carriers of MMP2 C-735T showed a significantly worse response. PFS was significantly prolonged in MMP1 G-1607GG variant allele carriers and OS in small cell lung cancer patients carrying the MMP12 A-82G variant allele. In conclusion, this study identified SNPs in MMP1, MMP2, MMP7 and MMP12 for further investigation as possible predictors of chemotherapy outcome in lung cancer patients
    Type of Publication: Journal article published
    PubMed ID: 19643940
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  • 8
    Keywords: pharmacology ; TRANSPORTER ; POLYMORPHISMS ; polymorphism ; chemotherapy ; CANCER-PATIENTS ; CANCER PATIENTS ; LUNG ; CANCER ; PATIENT ; LUNG-CANCER ; lung cancer ; GENES ; GENE
    Type of Publication: Meeting abstract published
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  • 9
    Keywords: NEW-YORK ; LUNG-CANCER ; GENE ; GENES ; PATIENT ; CANCER ; LUNG ; polymorphism ; POLYMORPHISMS ; chemotherapy ; pharmacology ; USA ; ARCH
    Type of Publication: Meeting abstract published
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  • 10
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    German Medical Science; Düsseldorf, Köln
    In:  15. Jahrestagung der Deutschen Gesellschaft für Thoraxchirurgie; 20060427-20060429; Weimar; DOC06dgt36 /20060426/
    Publication Date: 2006-04-27
    Keywords: asbestassozierte pleurale Befunde ; hochauflösende CT ; MRT ; Goldstandard ; ddc: 610
    Language: German
    Type: conferenceObject
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