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We recently found variants in cancer stem cell genes (CD44, ALCAM and LGR5) significantly associated with increased time to recurrence (TTR) in patients with stage III and high-risk stage II colon cancer treated with 5-fluorouracil (5-FU)-based chemotherapy. In this study, we validated these genetic biomarkers in a large and independent patient cohort (n=599). Patients who received 5-FU-based adjuvant chemotherapy (n=391) carrying at least one C allele in LGR5 rs17109924 had a significantly increased TTR compared with patients carrying the homozygous T/T variant (HR 0.38, 95%CI 0.19-0.79; P=0.006). In patients treated with surgery alone (n=208), no association between LGR rs17109924 and TTR was found (P=0.728). In the multivariate Cox-analysis, LGR5 rs17109924 remained statistically significant (HR 0.38, 95%CI 0.18-0.78; P=0.008) for patients who received adjuvant chemotherapy. We confirmed in a large and independent study cohort that LGR5 rs17109924 is a predictive genetic biomarker for TTR in patients with colon cancer treated with 5-FU-based adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Recent evidence indicates a potential prognostic and predictive value for germline polymorphisms in genes involved in cell cycle control. We investigated the effect of cyclin D1 (CCND1) rs9344 G>A in stage II/III colon cancer patients and validated the findings in an independent study cohort. For evaluation and validation set, a total of 264 and 234 patients were included. Patients treated with 5-fluorouracil-based chemotherapy, carrying the CCND1 rs9344 A/A genotype had significantly decreased time-to-tumor recurrence (TTR) in univariate analysis and multivariate analysis (hazard ratio (HR) 2.47; 95% confidence interval (CI) 1.16-5.29; P=0.019). There was no significant association between CCND1 rs9344 G>A and TTR in patients with curative surgery alone. In the validation set, the A allele of CCND1 rs9344 G>A remained significantly associated with decreased TTR in univariate and multivariate analyses (HR 1.94; 95% CI 1.05-3.58; P=0.035). CCND1 rs9344 G>A may be a predictive and/or prognostic biomarker in stage II/III colon cancer patients, however, prospective trials are warranted to confirm our findings. [ABSTRACT FROM AUTHOR]

Copyright of Strahlentherapie und Onkologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Strahlentherapie und Onkologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Summary Background Allergic symptoms are generally caused by exposure to substances to which people have become sensitized. Associated with this is an 'unbalanced' Th1/Th2 immune response with T cell responses skewed towards the production of Th2 cytokines, IL-4, 5, and 13 and high levels of IgE antibodies. Current immune modulating therapies require the use of allergens, carrying the risk to induce potentially severe allergic reactions. Objective Goal of the present study was to assess the safety and efficacy of an allergen-free immune modulator in patients suffering from perennial allergy. Methods In order to be protected from immediate degradation upon injection, a toll-like receptor 9 (TLR9) agonist was packaged into virus-like particles. These nanoparticles loaded with TLR9 ligands (CYT003-QbG10) were injected six times, at weekly intervals, into patients with house dust mite allergy in an attempt to ameliorate allergic symptoms by modifying the immune response towards allergens. Two different doses were compared against placebo in this double-blind, randomized phase IIb study ( n=299). Public trial registry: (NCT00800332). Results The treatment was safe and generally well tolerated. Rhinoconjunctivitis symptoms were significantly lower in patients treated with high dose of CYT003-QbG10 as compared with placebo (scores 0.31 vs. 0.52, P=0.04) based on a standardized average combined symptom and medication score. Furthermore, patients in the high dose group reported a significantly better quality of life score post-treatment than patients on placebo (scores 0.71 vs. 1.21, P=0.02). The conjunctival provocation test revealed a median 10-fold increase in allergen tolerance in the high dose group while in the placebo group it remained unchanged. Conclusion and Clinical Relevance Treatment with high-dose CYT003-QbG10 improved disease symptoms and reduced medication use in allergic individuals thus providing first evidence for a new potential immunotherapeutic. Cite this as: L. Klimek, J. Willers, A. Hammann-Haenni, O. Pfaar, H. Stocker, P. Mueller, W. A. Renner and M. F. Bachmann, Clinical & Experimental Allergy, 2011 (41) 1305-1312. [ABSTRACT FROM AUTHOR]

Purpose: Vascular endothelial growth factor (VEGF) is a potent regulator of angiogenesis and thereby involved in the development and progression of solid tumors. A 936C > T polymorphism in the VEGF gene has been associated with reduced VEGF plasma levels. Purpose of the present study was to analyze the potential association between VEGF genotype and radiological appearance of breast lesions by mammography. Materials and Methods: Fifty two women with 54 suspected breast lesions were analyzed by the use of mammography with the standard breast imaging reporting and data systems (BI-RADS). Germline VEGF genotype was determined in all subjects by allele-specific digestion of amplification products. An open biopsy was performed on all lesions. Results: VEGF CC, CT and TT genotypes were found in 41 (79%), 9 (17%) and 2 (4%) patients. By mammography 26, 16 and 12 suspected breast lesions were classified as BI-RADS scores 3, 4 and 5, respectively. Both carriers of the TT genotype were classified as BI-RADS 5, whereas among CT or CC carriers, BI-RADS scores 3, 4 and 5 were found in 26, 16 and 10 subjects (P < 0.026). Conclusion: The VEGF 936C > T polymorphism seems to be associated with a high BI-RADS score in women with suspicious breast lesions. [ABSTRACT FROM AUTHOR]

Purpose: Vascular endothelial growth factor (VEGF) is a potent regulator of angiogenesis and thereby involved in the development and progression of solid tumors. A 936C > T polymorphism in the VEGF gene has been associated with reduced VEGF plasma levels. Purpose of the present study was to analyze the potential association between VEGF genotype and radiological appearance of breast lesions by mammography. Materials and Methods: Fifty two women with 54 suspected breast lesions were analyzed by the use of mammography with the standard breast imaging reporting and data systems (BI-RADS). Germline VEGF genotype was determined in all subjects by allele-specific digestion of amplification products. An open biopsy was performed on all lesions. Results: VEGF CC, CT and TT genotypes were found in 41 (79%), 9 (17%) and 2 (4%) patients. By mammography 26, 16 and 12 suspected breast lesions were classified as BI-RADS scores 3, 4 and 5, respectively. Both carriers of the TT genotype were classified as BI-RADS 5, whereas among CT or CC carriers, BI-RADS scores 3, 4 and 5 were found in 26, 16 and 10 subjects (P < 0.026). Conclusion: The VEGF 936C > T polymorphism seems to be associated with a high BI-RADS score in women with suspicious breast lesions. [ABSTRACT FROM AUTHOR]

Adult-type hypolactasia, as mediated by a widespread genetic predisposition, not only reduces calcium intake but also calcium absorption in the presence of high amounts of lactose and may, therefore, promote osteoporosis. A lactose-reduced diet and lactose-free calcium supplements may reverse this imbalance. Adult-type hypolactasia (HL) defined by the LCT(−13910) polymorphism may reduce calcium intake by reducing dairy consumption and, therefore, promote osteoporosis. This study aimed to evaluate whether lactose also decreases intestinal calcium absorption in subjects with HL and whether lactose-reduced diet and lactose-free calcium supplementation as recommended could maintain bone mineral density (BMD). Based on LCT genotyping, 73 postmenopausal women with and without HL underwent a conventional H2 breath test with a concomitant oral strontium absorption test lasting 150 minutes, which closely reflects intestinal calcium absorption. In addition, we compared bone-specific laboratory parameters, lumbar and femoral BMD, and spinal radiographs to a similar bone assessment 5 years earlier. LCT genotyping and functional lactose malabsorption tests were highly correlated. Dairy product consumption was reduced by 80% in HL individuals. During concomitant lactose application, mean strontium absorption was blunted by 54% in HL subjects after 150 minutes (1272 ± 629 μg/L vs. 2020 ± 1130 μg/L in lactose tolerant subjects, p = 0.001). Nevertheless, BMD in HL subjects remained stable with lactose-free calcium supplements during the observation period. Both decreased calcium intake as well as lactose-associated impaired calcium absorption may predispose subjects with HL to osteoporosis. Lactose-free calcium supplementation may help to maintain BMD in HL subjects. [ABSTRACT FROM AUTHOR]

Nicotine increases serotonin release in the brain and symptoms of nicotine withdrawal may be modulated by diminished serotonergic neurotransmission. The promoter region of the serotonin transporter gene, solute carrier family neurotransmitter transporter member 4 (SLC6A4), contains a functional tandem repeat polymorphism. The long (L) variant is more actively transcribed than the short (S) variant and is associated with a higher serotonin uptake. To investigate the potential role of this polymorphism for smoking behavior, SLC6A4 genotypes were determined in two different studies, the SMOKING GENES case–control study (470 current smokers and 419 subjects who had never smoked) and the cross-sectional Ludwigshafen risk and cardiovascular health (LURIC) study (777 current smokers and 1178 subjects who had never smoked). In the SMOKING GENES case–control study, SLC6A4 genotype frequencies were not statistically different between smokers (LL: 30.9%; LS: 46.8%; SS: 16.4%) and non-smokers (LL: 36.3%; LS: 41.8%; SS: 14.3%; P=0.13). Similar results were obtained in the cross-sectional LURIC study (smokers: LL, 36.5%, LS, 45.6%, SS, 17.9%; non-smokers: LL, 33.6%, LS, 48.9%, SS, 17.6%; P=0.33). SLC6A4 genotypes were furthermore not associated with Fagerstrom Tolerance Questionnaire score, packyears, number of cigarettes smoked per day or previous attempts to quit smoking. We conclude that the SLC6A4 promoter polymorphism is not a major determinant of smoking behavior in Caucasian.The Pharmacogenomics Journal (2006) 6, 397–400. doi:10.1038/sj.tpj.6500389; published online 16 May 2006 [ABSTRACT FROM AUTHOR]

PurposePrimary open-angle glaucoma (POAG) is a multifactorial optic neuropathy with a strong hereditary component. Recent studies suggested a role for tumour necrosis factor-α(TNF-α) in the pathogenesis of POAG. The purpose of the present study was to investigate a hypothesized association between the TNF-α−308G>A and −238G>A gene polymorphisms and the presence of POAG in a Caucasian population.MethodsThe present case–control study comprised 114 unrelated patients with POAG and 228 healthy control subjects, matched for age and gender. Genotyping of the TNF-α−308G>A and −238G>A polymorphisms was performed using polymerase chain reaction.ResultsAllelic frequencies and genotype distributions of both the TNF-α−308G>A and −238G>A gene polymorphisms did not significantly differ between patients with POAG and control subjects. Presence of the TNF-α−308A-allele was associated with an odds ratio (OR) of 0.96 for POAG, whereas an OR of 0.52 was found among carriers of the TNF-α−238A-allele.ConclusionOur data suggest that none of the investigated TNF-αgene polymorphisms is a major risk factor among Caucasian patients with POAG.Eye (2006) 20, 1040–1043. doi:10.1038/sj.eye.6702078; published online 2 September 2005 [ABSTRACT FROM AUTHOR]

Purpose Retinal artery occlusion is a common vision-threatening disease. Among other risk factors, coagulopathies leading to a hypercoagulable state have been associated with retinal artery occlusion. Numerous studies have shown that two genetic variants, factor V Leiden and prothrombin 20210A, cause a procoagulant state. However, their role in the pathogenesis of retinal artery occlusion is still unclear. The purpose of the present study was therefore to investigate a possible association between factor V Leiden, prothrombin 20210A, and retinal artery occlusion.Methods In the present retrospective case-control study, we studied 136 patients with retinal artery occlusion and 136 age- and gender-matched control subjects. The presence of factor V Leiden and prothrombin 20210A alleles was determined by polymerase chain reaction.Results The prevalence of heterozygosity for the prothrombin G20210A variant did not significantly differ between patients and controls (three patients vs two controls, P=0.65). Distribution of factor V Leiden genotypes revealed no significant difference among the two groups (heterozygosity: eight patients vs 11 controls, P=0.47). As for other risk factors, arterial hypertension, a history of stroke and myocardial infarction were significantly more frequent in patients than in controls.Conclusion Our data suggest that factor V Leiden and prothrombin 20210A do not play a major role in patients with retinal artery occlusion.Eye (2003) 17, 731-734. doi:10.1038/sj.eye.6700495 [ABSTRACT FROM AUTHOR]

Abstract Objective Conflicting data exists about the possible contribution of the homozygous Asp/Asp genotype of the Glu298Asp polymorphism of endothelial nitric oxide synthase to human atherosclerotic vascular disease. We investigated the polymorphism in two independent study populations: a case–control study including patients with angiographically verified coronary artery disease (CAD) on the one hand and a cross-sectional epidemiological study on the other hand. Methods The Glu298Asp polymorphism was determined by PCR-RFLP as established. In the case–control study (240 patients and 248 controls) a possible association between the polymorphism and CAD, and age of onset of CAD and myocardial infarction was investigated. In the cross-sectional epidemiological study (932 subjects) intima-media thickness (IMT) of the carotid artery as well as morphological plaque burden and forearm vascular reactivity (peak postischemic reactive hyperaemia, determined by venous occlusion plethysmography) were measured. Results In the case–control study genotype distribution (Glu/Glu; Glu/Asp; Asp/Asp) was not different between the CAD patients (43/46/11%) and the controls (49/41/10%, P = NS). No association of the polymorphism with age of onset of CAD or myocardial infarction was found. In the epidemiological study no influence of the genetic variant on IMT was observed after correction for classical determinants of IMT (average IMT: Asp/ Asp: 0·077 ± 0·011 mm; Glu/Glu and Glu/Asp: 0·080 ± 0·012 mm, P = NS). Forearm vascular reactivity was also not different between homozygous Asp/Asp subjects and Glu/Glu and Glu/Asp subjects (peak-reactive hyperaemia 20·1 ± 7·3 mL min-1 100 mL-1 vs. 20·0 ± 6·5 mL min-1 100 mL-1 , P = NS). Conclusions Our results suggest that there is no association of the Glu298Asp polymorphism with coronary or carotid atherosclerosis or... [ABSTRACT FROM AUTHOR]

Abstract Background Elevated fibrinogen levels have been linked to increased risk for deep venous thrombosis, although it is not clear whether fibrinogen is causal or rather a marker for the presence of other risk factors. A common G/A polymorphism in the gene for the fibrinogen beta-chain (FGB G-455A) is associated with elevated fibrinogen levels. The present study was designed to analyze the role of this genetic marker for deep venous thrombosis. Materials and Methods We performed a case–control study including 307 patients with documented deep venous thrombosis and 316 control subjects. β-fibrinogen genotypes were determined by allele-specific polymerase chain reaction. Results GG, GA and AA genotype frequencies were similar among the patients (53·1%, 41·0, 5·9) and controls (51·6%, 42·1, 6·3; P = 0·92). Fibrinogen levels of the patients (median 3·72 g l-1 ; range 1·93–11·6) did not differ significantly from those of the controls (3·76; 2·17–9·99). Carriers of the homozygous AA genotype had significantly higher fibrinogen levels than noncarriers (patients: 5·32 vs. 3·59; P = 0·024; controls: 6·29 vs. 3·72; P = 0·048). Conclusion Our data suggest that the fibrinogen-elevating FGB G-455A gene polymorphism is not linked to an increased risk for deep venous thrombosis. [ABSTRACT FROM AUTHOR]

The nicotinamide adenine dinucleotide (NADH)/nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system is a major source of superoxide anion (·O2–) production in the human vasculature and may therefore influence lipid peroxidation and severity of atherosclerosis. This study aimed to investigate a hypothetical influence of the p22 phox C242T polymorphism on the generation of malondialdehyde (MDA), extent and clinical onset of coronary artery disease (CAD) in patients. We studied 108 male Caucasians with angiographically documented CAD and 45 controls free of vascular disease under 60 years of age. p22 phox C242T genotypes and MDA levels were determined. Additional information was obtained from each subject on classic risk factors and clinical events of CAD. Genotype distribution in CAD-patients and controls was thymine–thymine (TT): 13·8% (13·3%), cytosine–thymine (CT): 46·3% (53·3%) and cytosine–cytosine (CC): 39·8% (33·3%), respectively. No significant influence was seen of the p22 phox C242T polymorphism on corresponding mean MDA levels in both groups. Furthermore, age at onset of first time angina pectoris (AP) and myocardial infarction (MCI) was not significantly different between genotype groups. It is concluded that the C242T polymorphism of the p22 phox gene is not associated with lipid peroxidation as measured by MDA, and is not a genetic risk marker for CAD Caucasians. [ABSTRACT FROM AUTHOR]

The relationship of three types of personal conflict and clinical symptoms was examined in a group of 139 psychotherapy clients and participants of a psychological training course in the workplace. The participants received the Lauterbach conflict measure and the Symptom Checklist (SCL-90-R). A subgroup of low-conflict and a subgroup of high-conflict participants was formed. Conflict measures and clinical symptoms were highly correlated in the low-conflict group, but not in the high-conflict group. In addition, we showed that the three types of cognitive conflict correlated highly in low-conflict participants but not in the high-conflict subgroup. We concluded that symptoms and conflict account for different dimensions of mental strain in highly conflicted individuals and personal conflict represents a risk factor for developing clinical symptoms. Psychotherapy should not be limited to the symptom dimension but should account for the conflict perspective in an individualized approach. [ABSTRACT FROM PUBLISHER]

The administrative process in the implementation of a scheme of co-operation between the school and general dental practitioner services to screen and treat children aged 14 years and above in an Area Health Authority is described. 84 % of the target group were screened in periods amounting to 12 months. The uptake of treatment as assessed by return of notices of referral was only 1.5 %. Interview of a sample of those referred revealed that 49 % had been to a dentist within 6 months and of these 34 % would not have otherwise attended, 13 % had taken referral forms to practitioners. The implications of these findings are discussed and a more effective means of evaluating treatment uptake is proposed. [ABSTRACT FROM AUTHOR]

Damages to inner ear function can be induced by improper application of ear drops. Which of the many substances combined in commercial otological preparations is mainly responsible, still remains a matter of controversy. In guinea pigs a defined amount of different ear drops is applied to the round window over a constant time period and, at the same time, the inner ear function is determined by continuous recording of the compound action potentials and cochlear microphonics. In this way, the relative intratympanic ototoxicity of neomycin and tetracain concentration series can be compared with commercial aminoglycoside containing ear drops. However, there are some ear drops which contain highly ototoxic substances, they show no significant differences of hearing loss to other. [ABSTRACT FROM AUTHOR]