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  • CANCER  (12)
  • 1
    Keywords: CANCER ; IN-VITRO ; tumor ; CELL ; COMBINATION ; Germany ; human ; THERAPY ; VIVO ; DRUG ; TUMORS ; SURGERY ; radiation ; PATIENT ; MALIGNANCIES ; chemotherapy ; SQUAMOUS-CELL CARCINOMA ; HEAD ; CROSS-RESISTANCE ; NECK ; ARTIFACTS ; head and neck ; ELIMINATION ; MANAGEMENT ; NECK-CANCER ; INDUCTION CHEMOTHERAPY ; MALIGNANCY ; PROGRAM ; review ; head and neck cancer ; THERAPIES ; ORGAN PRESERVATION ; ADVANCED LARYNGEAL-CANCER ; DRUG-RESPONSE ASSAY ; SENSITIVITY ASSAYS ; chemosensitivity ; EX-VIVO ; chemosensitivity assays ; COLONY-FORMING ASSAY ; predictive tests ; SOFT-AGAR ; SOLID TUMORS
    Abstract: Despite many advances in predictive testing of human malignancies, we are far from using it routinely in clinical practice. Investigating the responsiveness of solid tumors to cytostatic drugs is particularly challenging. Nevertheless, for head and neck cancer, chemosensitivity testing is an increasingly attractive option, since chemotherapy has proven to have curative potential in the therapy of head and neck cancer, in particular in combination with radiation. The significant need for predictive methods to identify patients responsive to therapy, first of all in organ preservation programs, which is an alternative to first-line surgery, had recently renewed the discussion on a possible role of chemosensitivity testing in head and neck cancer. In this review, we discuss the current state of chemosensitivity testing in head and neck cancer. Recent methodological developments, in particular elimination of photochemical artifacts and inclusion of stromal cell response studies, may soon augment the value of ex vivo chemosensitivity testing for the management of head and neck cancer
    Type of Publication: Journal article published
    PubMed ID: 15249723
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  • 2
    Keywords: CANCER ; CELLS ; tumor ; carcinoma ; Germany ; THERAPY ; TUMORS ; PATIENT ; treatment ; 5-FLUOROURACIL ; ASSAY ; chemotherapy ; EPITHELIAL-CELLS ; HEAD ; NECK ; squamous cell carcinoma ; PREDICTION ; sensitivity ; head and neck carcinoma ; HNSCC ; INFUSION ; SOLID TUMORS ; COLONY FORMATION ; chemosensitivity testing ; head and neck squamous cell carcinoma ; SPECIMENS ; 5-FU ; drug combinations ; tumor stroma
    Abstract: Previous studies focusing on response prediction to chemotherapy by chemosensitivity testing of tumor explants has focused on the response determination of single cytostatic drugs, in contrast to the common clinical application of cytostatic drug combinations. Therefore, the present study was aimed at determining the quantitative ex vivo chemoreactivity of epithelial cells from head and neck squamous cell carcinoma (HNSCC) specimens to cytostatic drug combinations. Specimens from 12 histologically-confirmed HNSCC were investigated. According to a previously established ex vivo colony formation assay, the individual cellular chemoreactivity was determined quantitatively for combinations of 4 cytostatic drugs: cis-platinum (cis-DDP), carboplatin (CBDCA), 5-Fluorouracil (5-FU) and docetaxel (DTX). The tests were performed using drug combinations according to recent clinical therapy regimens in the treatment of solid tumors: i) cis-DDP + 5FU, ii) CBDCA + 5FU, iii) cis-DDP + DTX and iv) CBDCA + DTX The approach provides individual drug response patterns of epithelial as well as of stromal cells. Individual, selective sensitivities were found for each drug combination tested. The stromal and epithelial chemoreactivity profiles differed in most of the specimens. Moreover, stromal cell chemoresistance dominated selective epithelial chemosensitivities in the majority of cases. The determination of the epithelial ex vivo chemoreactivity identified individual chemosensitivities which were verified by the clinical history of the patient. Therefore, the described protocol to determine the ex vivo chemoresponse of HNSCC specimens to cytostatic drug combinations may help to provide clinicaly useful information concerning the individual chemoresponse of HNSCC with regard to individualization of oncological decision making
    Type of Publication: Journal article published
    PubMed ID: 16619587
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  • 3
    Keywords: CANCER ; carcinoma ; Germany ; LUNG-CANCER ; EXPOSURE ; HISTORY ; MORTALITY ; NEW-YORK ; POPULATION ; RISK ; WORKERS ; PATIENT ; RISK-FACTORS ; FREQUENCY ; score ; AGE ; risk factors ; smoking ; MALES ; cancer risk ; RISK FACTOR ; REGION ; HEAD ; NECK ; case-control studies ; TOBACCO ; ALCOHOL ; QUESTIONNAIRE ; INDUSTRY ; laryngeal carcinoma,occupational exposure,construction industry,epidemiology,cement dust
    Abstract: A population-based case-control study was performed in the Rhein-Neckar region, Germany, to evaluate occupational risk factors for the development of laryngeal cancer ("Rhein-Neckar-Larynx Study"). Between May 1998 and December 2000, 257 patients (236 males, 21 females), aged 37-80, with histologically confirmed laryngeal cancer, as well as 769 population control persons (702 males, 67 females), were included (1:3 frequency matched by age and sex). History of occupational exposures, as well as other risk factors (tobacco, alcohol), was obtained with face-to-face interviews using a detailed standardized questionnaire. The complete individual work history was assessed. A detailed assessment of work conditions was obtained by job-specific questionnaires (JSQs) for selected jobs known to be associated with exposure to potential laryngeal carcinogens. Estimates for total exposure hours by substance were calculated based on JSQs. Published occupational hygiene data were used to infer semiquantitative scores of exposure intensity for specific job tasks. After adjustment for tobacco and alcohol intake, a significant elevated odds ratios (OR) could be demonstrated for persons that were exposed to cement during their work as building and construction workers. An OR of 2.42 was calculated for workers of the high exposed subgroup (95% confidence interval: 1.14-5.15; p 〈 0.001). Smoking was the main confounding factor because the unadjusted cement OR of 3.20 dropped down to 2.42 after adjustment for tobacco intake. We conclude that there is good evidence for cement dust exposure acting as a tobacco, alcohol and asbestos independent risk factor for laryngeal carcinoma. Our study gives a base for further toxicologic investigations on this topic. (C) 2003 Wiley-Liss, Inc
    Type of Publication: Journal article published
    PubMed ID: 14712496
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  • 4
    Keywords: CANCER ; EXPRESSION ; tumor ; carcinoma ; COMBINATION ; Germany ; DISEASE ; DISEASES ; CDNA ; GENE ; GENE-EXPRESSION ; GENES ; microarray ; PROTEIN ; PROTEINS ; DIFFERENTIATION ; TISSUE ; FAMILY ; CONTRAST ; KERATINOCYTES ; SKIN ; DYNAMICS ; IDENTIFICATION ; PROGRESSION ; immunohistochemistry ; PATTERNS ; gene expression ; microarrays ; MEMBRANE ; mass spectrometry ; MASS-SPECTROMETRY ; cytoskeleton ; HEAD ; NECK ; squamous cell carcinoma ; CDNA MICROARRAYS ; CDNA MICROARRAY ; MASSES ; keratinocyte ; HNSCC ; ULTRAVIOLET ; S100 PROTEINS ; transcript ; CELL-CARCINOMA ; EXPRESSION PATTERNS ; ENVELOPE ; protein biomarkers ; S100 and annexin protein family ; SELDI-TOF MS
    Abstract: The calcium-binding proteins of the S100 and the annexin protein families have been implicated in a variety of important physiological functions including membrane remodeling, calcium-related Intracellular signaling, cytoskeleton dynamics. tissue homeostasis, and formation of the cornified envelope in differentiating keratinocytes. Deregulated expression of members of these families has been reported in different types of neoplasia and other diseases, but the results were not consistent. Here we have applied a combination of cDNA microarrays, quantitative reverse transcriptase-PCR (qRT-PCR) and surface enhanced laser desorption ionisation-time of flight mass spectrometry (SELDI-TOF MS) to Study differential expression of these genes in head and neck squamous cell carcinoma (HNSCC). The calgranulins A and B and annexins 1 and 2 were found to be down-regulated in HNSCC, compared with normal mucosa, at both the mRNA and protein level. Upon validation of the differential gene expression by tissue microarray immunohistochemistry, we detected novel expression patterns of calgranulins A and B both in normal mucosa as well as in HNSCC. In contrast to squamous cancer of skin and other cancers in which the calgranulins were found to be up-regulated, most HNSCC showed reduced and widely deranged staining patterns including heterogeneous nuclear, cytoplasmic and membranous staining, and even enhanced staining in the tumor stroma. These observations suggest that the normal function of the calgranulins A and B in mucosa might be different from that in skin. (c) 2005 Elsevier GmbH. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 15819419
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  • 5
    Keywords: CANCER ; EXPRESSION ; INHIBITOR ; tumor ; carcinoma ; CELL ; Germany ; CLASSIFICATION ; DIAGNOSIS ; RISK ; PROTEIN ; SAMPLES ; PATIENT ; BIOLOGY ; ASSOCIATION ; FIELD ; ALPHA ; STAGE ; IDENTIFICATION ; IN-SITU ; immunohistochemistry ; genetics ; ABERRATIONS ; MASS-SPECTROMETRY ; ONCOGENE ; HUMAN-PAPILLOMAVIRUS ; SQUAMOUS-CELL CARCINOMA ; HEAD ; NECK ; RISK ASSESSMENT ; heredity ; BIOPSY ; protein expression ; PROTEOMICS ; PROTEOMIC ANALYSIS ; NECK-CANCER ; CELL CARCINOMA ; ONCOLOGY ; TUMORIGENESIS ; ARRAY ; HNSCC ; LYMPH-NODE METASTASIS ; development ; analysis ; PROFILES ; EVENTS ; protein biomarkers ; HISTOLOGY ; FRAGMENT ; SELDI-TOF-MS ; BIOPSIES ; CLINICAL-IMPLICATIONS ; aberration ; comparison ; acyl-CoA-binding protein ; CANCERIZATION ; field cancerization ; GENETICALLY ALTERED FIELDS ; HUMAN NEUTROPHIL PEPTIDE-1 ; TUMOR-DISTANT EPITHELIA
    Abstract: Development of head and necksquamous cell carcinoma (HNSCC) is a multistep process and in many cases involves a phenomenon coined 'field cancerization'. In order to identify changes in protein expression occurring at different stages of tumorigenesis and field cancerization, we analysed 113 HNSCCs and 73 healthy, 99 tumor-distant and 18 tumor-adjacent squamous mucosae by SELDI-TOF-MS on IMAC30 ProteinChip Arrays. Forty-eight protein peaks were differentially expressed between healthy mucosa and HNSCC. Calgizarrin (S100A11), the Cystein proteinase inhibitor Cystatin A, Acyl-CoA-binding protein, Stratifin (14-3-3 sigma), Histone H4, alpha- and beta-Hemoglobin, a C-terminal fragment of beta-hemoglobin and the alpha-defensins 1-3 were identified by mass spectrometry. The alpha-defensins showed various alterations in expression as validated by immunohistochemistry (IHC). Supervised prediction analysis revealed excellent classification of healthy mucosa (94.5% correctly classified) and tumor samples (92.9% correctly classified). Application of this classifier to the tumor-adjacent and tumor-distant mucosa samples disclosed dramatic changes: only 59.6% of the tumor-distant biopsies were classified as normal, 27.3% were predicted as aberrant or HNSCC. Strikingly, 72% of the tumor-adjacent mucosae were predicted as aberrant. These data provide evidence for the existence of genetically altered fields with inconspicuous histology. Comparison of the protein profiles in the tumor-distant-samples with clinical outcome of 32 patients revealed a significant association between aberrant profiles with tumor relapse events (P = 0.018; Fisher's exact test, two-tailed). We conclude that proteomic pro. ling in conjunction with protein identification greatly outperforms histopathological diagnosis and may have significant predictive power for clinical outcome and personalized risk assessment
    Type of Publication: Journal article published
    PubMed ID: 16819514
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  • 6
    Keywords: CANCER ; radiotherapy ; tumor ; carcinoma ; Germany ; THERAPY ; DIAGNOSIS ; QUANTIFICATION ; DISEASE ; METABOLISM ; radiation ; PATIENT ; primary ; TRIAL ; TRIALS ; chemotherapy ; positron emission tomography ; POSITRON-EMISSION-TOMOGRAPHY ; tomography ; SQUAMOUS-CELL CARCINOMA ; GLUCOSE ; PET ; sensitivity ; laryngeal carcinoma ; RECONSTRUCTION ; NECK-CANCER ; THERAPIES ; ADVANCED HEAD ; chemoradiation ; FDG PET ; hypopharyngeal carcinoma ; larynx organ preservation ; ORGAN PRESERVATION ; RESIDUAL DISEASE
    Abstract: Patients and methods. In a group of 20 patients undergoing chemoradiation for larynx organ preservation after diagnosis of laryngeal and hypopharyngeal carcinoma, F-18-fluordeoxyglucose positron emission tomography (F-18-FDG-PET) was performed before the start of therapy. After i.v.application of 240 MBq FDG, a dynamic PET in 3-D-mode was performed over 90 min (Siemens CTI ECAT EXACT HR+). Analysis was done visually and semiquantitatively (60-90 min p.i.) following iterative reconstruction. Additional F-18-FDG-PET investigations were done and correlated with the clinical outcome in 16/20 patients at 3 months and in 14/20 patients at 6 months after the end of therapy. Results. In 17/20 patients (85%), the preclinical F-18-FDG-PET correlated well with the histologically confirmed primary tumor. Three cases were false negatives. In one case this was due to an increased glucose value (203 mg%). After 3 months, 8/13 (62%) patients showed a positive correlation between clinical and PET results (sensitivity 100%, specificity 70%). After 6 months, 9/11 (82%) patients presented clinically normal PET results. PET results were false negative in one case (sensitivity 67%, specificity 88%). Conclusion. The data of our trial slightly reduce the enthusiasm of early F-18-FDG-PET detection of residual disease after chemoradiation in resectable laryngeal or hypopharyngeal cancer. Further trials should optimize the calculation integrating the exact quantification of glucose metabolism with the aim of improving sensitivity and specificity
    Type of Publication: Journal article published
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  • 7
    Keywords: CANCER ; AGENTS ; BLOOD ; Germany ; LUNG-CANCER ; EXPOSURE ; HISTORY ; MORTALITY ; occupation ; POPULATION ; RISK ; RISKS ; RISK-FACTORS ; FREQUENCY ; NUMBER ; AGE ; risk factors ; smoking ; cancer risk ; DOSE-RESPONSE ; SQUAMOUS-CELL CARCINOMA ; gene-environment interaction ; case-control studies ; TOBACCO ; ALCOHOL ; QUESTIONNAIRE ; questionnaires ; glutathione-S-transferase ; OCCUPATIONAL EXPOSURE ; AGENT ; case-control study ; population-based case-control study ; EMISSIONS ; CARCINOGEN ; laryngeal cancer ; GSTM1 ; GSTT1 ; case control studies ; INTERVAL ; GENOTYPE ; ADJUSTMENT ; duration ; GENDER ; glutathione-S-transferases ; road construction workers
    Abstract: Primary risk factors for laryngeal cancer are smoking and alcohol. The relevance of occupational exposures in the etiology of laryngeal cancer is not yet clarified. Some studies have suggested various occupational agents as additional causal risk factors. A population-based case-control study 1:3 frequency matched by age and gender on laryngeal cancer was carried out in southwest Germany with 257 cases (236 males and 21 females between the ages of 37-80, histologically confirmed and diagnosed between January 5, 1998 and December 31, 2000) and 769 population controls (702 males, 67 females). Occupational exposures and other risk factors were obtained with face-to-face interviews using a detailed standardized questionnaire. The complete individual work history was assessed. A detailed assessment of work conditions was obtained by job-specific questionnaires for selected jobs known to be associated with exposure to potential carcinogens. A specific substance list was used as second method for exposure assessment. Blood samples were taken from all individuals for genotype analysis. A strong effect of polycyclic aromatic hydrocarbons exposure on laryngeal cancer risk after adjustment for smoking and alcohol (odds ratio [OR] = 5.2, 95% confidence interval [CI] = 1.6-17.1) was observed for concordant exposure classified with both methods, and a clear dose-response (p 〈 0.01 for linear trend) for exposure duration. Our findings are supported by risks associated with occupational groups in which this exposure is a priori considered likely. A differential effect by glutathione-S-transferases-M1 genotype was found, however, small numbers do not allow firm conclusions on effect modification. Our study contributes to classifying polycyclic aromatic hydrocarbons as a risk factor for laryngeal cancer. (C) 2005 Wiley-Liss, Inc
    Type of Publication: Journal article published
    PubMed ID: 15810012
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  • 8
    Keywords: RECEPTOR ; APOPTOSIS ; CANCER ; HISTORY ; RISK ; SAMPLE ; TUMOR-NECROSIS-FACTOR ; FAMILY ; BIOMARKERS ; ASSOCIATION ; polymorphism ; POLYMORPHISMS ; single nucleotide polymorphism ; FREQUENCIES ; BREAST ; breast cancer ; BREAST-CANCER ; HEALTH ; AGE ; WOMEN ; SNP ; cancer risk ; GENOTYPES ; HETEROGENEITY ; FAMILIES ; VARIANT ; SINGLE NUCLEOTIDE POLYMORPHISMS ; ESTROGEN ; SINGLE-NUCLEOTIDE POLYMORPHISMS ; ALLELES ; biomarker ; GENOTYPE ; FAMILY-HISTORY ; USA ; CANCER-RISK ; Sample Size ; CONSORTIUM ; ERCC4 ; RECEPTOR STATUS ; PROGESTERONE-RECEPTOR GENE ; CASP8
    Abstract: Previous studies have suggested that minor alleles for ERCC4 rs744154, TNF rs361525, CASP10 rs13010627, PGR rs1042838, and BID rs8190315 may influence breast cancer risk, but the evidence is inconclusive due to their small sample size. These polymorphisms were genotyped in more than 30,000 breast cancer cases and 30,000 controls, primarily of European descent, from 30 studies in the Breast Cancer Association Consortium. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) as a measure of association. We found that the minor alleles for these polymorphisms were not related to invasive breast cancer risk overall in women of European descent: ECCR4 per-allele OR (95% CI) = 0.99 (0.97-1.02), minor allele frequency = 27.5%; TNF 1.00 (0.95-1.06), 5.0%; CASP10 1.02 (0.98-1.07), 6.5%; PGR 1.02 (0.99-1.06), 15.3%; and BID 0.98 (0.86-1.12), 1.7%. However, we observed significant between-study heterogeneity for associations with risk for single-nucleotide polymorphisms (SNP) in CASP10, PGR, and BID. Estimates were imprecise for women of Asian and African descent due to small numbers and lower minor allele frequencies (with the exception of BID SNP). The ORs for each copy of the minor allele were not significantly different by estrogen or progesterone receptor status, nor were any significant interactions found between the polymorphisms and age or family history of breast cancer. In conclusion, our data provide persuasive evidence against an overall association between invasive breast cancer risk and ERCC4 rs744154, TNF rs361525, CASPIO rs13010627, PGR rs1042838, and BID rs8190315 genotypes among women of European descent. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1610-6)
    Type of Publication: Journal article published
    PubMed ID: 19423537
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  • 9
    Keywords: CANCER ; carcinoma ; PHARYNX ; RISK ; DNA ; RISK-FACTORS ; GENETIC POLYMORPHISMS ; tumour ; ASSOCIATION ; SUSCEPTIBILITY ; AGE ; risk factors ; smoking ; PCR ; LYMPHOCYTES ; genotyping ; LINKAGE DISEQUILIBRIUM ; SQUAMOUS-CELL CARCINOMA ; HEAD ; TOBACCO ; ALCOHOL ; alcohol dehydrogenase ; laryngeal carcinoma ; ORAL CAVITY ; M1 ; glutathione-S-transferase ; ALCOHOL-DEHYDROGENASE-3 GENOTYPE ; CHINESE PATIENTS ; molecular epidemiology ; NECK- CANCER ; tobacco and alcohol associated risk
    Abstract: Objective Alcohol and tobacco consumption are recognized risk factors for upper aerodigestive tract tumours, however individual susceptibility to these environmental factors varies. As part of the Rhein-Neckar Larynx-case-control study, this study investigated the potential risk-modifying effect of genetic polymorphisms in enzymes involved in ethanol and tobacco carcinogen metabolism for laryngeal cancer in Germany. Methods Two hundred and forty-five cases and 251 population- based controls, matched by age and gender, were genotyped for genetic polymorphisms in ADH1B, ADH1C, GSTM1 and GSTT1, using genomic DNA isolated from peripheral lymphocytes and employing PCR and PCR/restriction fragment length polymorphism-based methods. Results Neither the putative risk genotypes ADH1B*21* 1 (OR 0.86, 95% confidence interval (CI): 0.41-1.82) or ADH1C* 1/* 1 (OR 1.06, CI 0.7-1.62) nor GSTM1 null (OR 0.94, CI 0.62- 1.42) or GSTT1 null (OR 1.34, CI 0.74-2.42) were associated with an overall increased risk for laryngeal cancer. Stratified analyses were carried out to determine the gene-environment interaction in relation to laryngeal cancer risk. However, ADH1B or ADH1C genotypes did not markedly modify the risk observed after stratification by alcohol consumption, and stratification by cumulative smoking exposure (in packyears) did not show an association of GSTM1 or GSTT1 genotype with laryngeal carcinoma either. Conclusion The lack of risk modification by the studied genotypes emphasizes the importance of environmental exposure to tobacco smoke and alcohol as major risk factors for laryngeal cancer in the German study population
    Type of Publication: Journal article published
    PubMed ID: 12668919
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  • 10
    Keywords: CANCER ; CELLS ; EXPRESSION ; tumor ; TUMOR-CELLS ; carcinoma ; CELL ; evaluation ; Germany ; VIVO ; DRUG ; PATIENT ; TRANSPORT ; TRIAL ; ASSAY ; chemotherapy ; HEAD ; NECK ; squamous cell carcinoma ; GLUCOSE ; sensitivity ; GREECE ; head and neck ; METABOLITE ; PHASE-II ; AGENT ; targeting ; CELL CARCINOMA ; chemosensitivity ; D-19575 ; D-GLUCOSYLISOPHOSPHORAMIDE MUSTARD ; EUROPEAN ORGANIZATION ; EX-VIVO ; glufosfamide ; head and neck carcinoma ; HNSCC ; INFUSION ; TRANSPORTER
    Abstract: Background: Glufosfamide is a novel alkylating agent in which the active metabolite of isophosphoramide mustard is glycosidically linked to beta-D-glucose. Targeting the elevated glucose uptake of tumor cells expressing the SAAT1 glucose transporter, glufosfamide represents an attractive new drug for cancer chemotherapy. The present study investigates the ex vivo responsiveness of Head and Neck Squamous Cell Carcinoma (HNSCC) specimens to glufosfamide. Patients and Methods: Twenty-one unselected HNSCC specimens were investigated using a novel ex vivo colony formation assay to determine the epithelial drug response. The individual responsiveness to glufosfamide and to cis-platinum was determined. Results: Five out of 21 evaluable HNSCC specimens were sensitive to glufosfamide. There was a tendency for glufosfamide sensitivity in platinum-resistant specimens and vice versa. Conclusion: The effectiveness of glufosfamide observed in the present ex vivo study suggests at least an equipotentiality of glufosfamide in comparison to cis-platinum. The potential clinical usefulness of glufosfamide in HNSCC warrants further evaluation
    Type of Publication: Journal article published
    PubMed ID: 15517901
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