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  • 1
    Keywords: CELLS ; BLOOD ; CELL ; COMBINATION ; Germany ; THERAPY ; DISEASE ; RISK ; DRUG ; TIME ; PATIENT ; CYCLE ; treatment ; STAGE ; TRIAL ; TRIALS ; LYMPHOMA ; NUMBER ; REDUCED RISK ; RATES ; chemotherapy ; PCR ; PROBES ; CLEARANCE ; PERIPHERAL-BLOOD ; FOLLICULAR LYMPHOMA ; MINIMAL RESIDUAL DISEASE ; NON-HODGKINS-LYMPHOMA ; CAPACITY ; RESIDUAL DISEASE ; ANTI-CD20 MONOCLONAL-ANTIBODY ; rituximab ; REMISSION ; prospective ; COMBINATION THERAPY ; E ; B-CELL ; peripheral blood ; nested PCR ; t(14 ; 18) ; molecular monitoring ; RQ-PCR ; t(14 : 18)
    Abstract: Accurate monitoring of the t(14; 18) translocation is regarded as highly desirable in patients with follicular lymphoma (FL) as absence of bcl-2/IgH positive cells has been correlated with a reduced risk of recurrence and, more recently, pre-treatment t(14;18) load with response to rituximab (R: Blood 2004; 103:4416-23). With the arrival of R clinical and molecular remission rates for various lymphoma entities improved significantly, creating the need to carefully review and reassess the role of PCR negativity for clinical outcome, specifically when considering the prolonged presence of the drug as compared to chemotherapy. To determine the rate of molecular clearance achieved by the addition of different doses of R 16 newly diagnosed, t(14;18) positive patients with FL (Ann Arbor stages III/IV) were investigated before, during and after primary chemotherapy with six cycles of CHOP combined with varying (1, 3 or 6) cycle numbers of R (varR1-, varR3- or varR6-CHOP, respectively) regarding molecular remission status. For this purpose classic nested PCR as well as a newly established RQ-PCR employing juxtaposed hybridisation probes were employed to assess molecular remission prior, during and post therapy. Interestingly, administering just a single cycle of R (varR1-CHOP) in combination with a standard regimen of CHOP resulted in rapid and effective clearance of t(14;18) carrying cells from the peripheral blood of 4/5 patients in this treatment group. 6/8 (6/8) varR1-/varR3-CHOP patients were fully cleared and 8/8 (7/8) var6-CHOP patients as assessed by RQ- (nested) PCR. This indicates the high clearance capacity of this combination therapy approach even when adding a very low cycle number of R (1 and 3, respectively) to CHOP in primary therapy of FL. In summary, the relationship established between molecular clearance and minimal residual disease/risk of recurrence may have to be redefined in the times of R. Upcoming large prospective trials will have to elucidate to what degree the clearance of peripheral blood from t(14;18) positive cells can still be regarded as informative regarding absence of minimal residual disease, remission status and/or risk of recurrence. (c) 2006 Elsevier Ltd. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 16530831
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  • 2
    Keywords: CANCER ; Germany ; COMMON ; POPULATION ; RISK ; GENE ; SAMPLE ; PATIENT ; SKIN ; SEQUENCE ; ASSOCIATION ; polymorphism ; POLYMORPHISMS ; single nucleotide polymorphism ; BREAST-CANCER ; NO ; MUTATION ; ACUTE LYMPHOBLASTIC-LEUKEMIA ; MELANOMA ; PATHOGENESIS ; REGION ; MALIGNANT-MELANOMA ; MELANOMA PATIENTS ; malignant melanoma ; SUSCEPTIBILITY GENE ; SINGLE ; molecular ; ONCOLOGY ; ASSOCIATIONS ; RE ; SINGLE NUCLEOTIDE POLYMORPHISMS ; analysis ; HAPLOTYPE ; HAPLOTYPES ; single-nucleotide ; PREDISPOSITION ; USA ; VITAMIN-D-RECEPTOR ; MEDICINE ; case control ; German ; case-control ; association study ; genetic analysis ; DNA-DAMAGE RESPONSE ; GERMLINE 657DEL5 MUTATION ; NBS1 ; NIJMEGEN-BREAKAGE-SYNDROME
    Abstract: The aim of this study was to investigate the role of NBS1 in the pathogenesis of malignant melanoma of the skin. To exclude the common 657del5 founder mutation, a total of 376 melanoma patients from Southern Germany were analyzed for sequence alterations in exon 6 of NBS1 by direct sequencing. Analyses revealed one 657del5 mutation and three nonsynonymous sequence variations in exon 6 of NBS1 (V210F, R215W, and F222L). Analysis of an additional sample of 629 melanoma patients and 604 controls revealed no F222L mutation, indicating that this newly identified sequence alteration is not a common polymorphism. In a case-control association study including 632 melanoma patients and 615 cancer-free control participants from Southern Germany, three publicly known single nucleotide polymorphisms located in the NBS1 gene region were analyzed. No significant associations between single nucleotide polymorphisms (rs9995, rs867185 and rs1063045) or referring calculated haplotypes and melanoma risk were identified. These results suggest that NBS1 does not play a major role in predisposition to melanoma in the Southern German population but that alterations of this gene might contribute to the risk of this cancer
    Type of Publication: Journal article published
    PubMed ID: 17496786
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  • 3
    Keywords: CANCER ; tumor ; Germany ; RISK ; GENE ; PATIENT ; IMPACT ; ASSOCIATION ; polymorphism ; VARIANTS ; BREAST ; breast cancer ; BREAST-CANCER ; MELANOMA ; TUMOR-SUPPRESSOR GENE ; cancer risk ; HIGH-RISK ; INDIVIDUALS ; familial cancer ; BREAST-CANCER RISK ; RE ; TUMOR-SUPPRESSOR ; VARIANT ; ENHANCEMENT ; tumor suppressor gene ; INCREASED RISK ; CANCER-RISK ; FAMILIAL BREAST ; familial breast cancer ; ARLTS1 ; multiple melanomas
    Abstract: Variants in the tumor suppressor gene ARLTS1 (ADP-ribosylation factor-like tumor-suppressor gene 1) have been shown to influence familial cancer risk. Both Cys148Arg and Trp149Stop were associated with an increased risk of familial or high-risk familial breast cancer, respectively. We studied the impact of these gene variants on melanoma risk, investigating 351 melanoma patients and 804 control subjects. While ARLTS1 Trp149Stop did not influence melanoma risk (OR = 0.83, 95% CI = 0.37-1.88, p = 0.65), Cys148Arg revealed a statistically significant association with an increased risk for heterozygous carriers (OR = 1.43, 95% CI = 1.05-1.95, p = 0.02). An additional risk enhancement, though statistically non-significant, was observed in individuals with multiple melanomas (OR = 2.33, 95 % CI = 0.87-6.26, p = 0.08). (c) 2006 Wiley-Liss, Inc
    Type of Publication: Journal article published
    PubMed ID: 16646072
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