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  • DKFZ Publication Database  (1,346)
  • RE  (1,346)
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  • DKFZ Publication Database  (1,346)
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  • 1
    Keywords: tumor ; incidence ; TUMORS ; DISORDER ; SWEDEN ; TRENDS ; DISORDERS ; RE ; MYELOPROLIFERATIVE DISORDERS
    Type of Publication: Journal article published
    PubMed ID: 18501963
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  • 2
    Keywords: molecular ; molecular biology ; aging ; RE ; MITOCHONDRIA ; MOLECULAR-BIOLOGY ; BIOLOGY ; ENGLAND
    Type of Publication: Meeting abstract published
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  • 3
    Keywords: CELLS ; CANCER ; tumor ; TUMOR-CELLS ; CELL ; TISSUES ; TISSUE ; RE ; METASTASIS ; TARGET
    Type of Publication: Meeting abstract published
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  • 4
    Keywords: COLORECTAL-CANCER ; PROSPECTIVE COHORT ; colorectal cancer ; RECURRENCE ; ONCOLOGY ; RE ; CANCER ; COHORT ; PATIENT ; flavonoid ; comparison ; prospective
    Type of Publication: Meeting abstract published
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  • 5
    Keywords: CANCER ; EXPRESSION ; E-cadherin ; RE ; GASTRIC-CANCER ; LOSSES ; gastric cancer ; correlates
    Type of Publication: Meeting abstract published
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  • 6
    Keywords: ANGIOGENESIS ; CELLS ; ENDOTHELIAL-CELLS ; GROWTH-FACTOR ; CELL ; Germany ; human ; IN-VIVO ; DISTINCT ; DIFFERENTIATION ; TISSUE ; MICE ; COMPLEX ; cytokines ; MOUSE ; ASSAY ; IMMUNODEFICIENT MICE ; EMBRYONIC STEM-CELLS ; RE ; BLOOD-VESSELS ; analysis ; methods ; ASSAYS ; progenitor ; ENGLAND ; modification ; three-dimensional ; LIMITS
    Abstract: The complexity of the angiogenic cascade limits cellular approaches to studying angiogenic endothelial cells (ECs). In turn, in vivo assays do not allow the analysis of the distinct cellular behavior of ECs during angiogenesis. Here we show that ECs can be grafted as spheroids into a matrix to give rise to a complex three-dimensional network of human neovessels in mice. The grafted vasculature matures and is connected to the mouse circulation. The assay is highly versatile and facilitates numerous applications including studies of the effects of different cytokines on angiogenesis. Modifications make it possible to study human lymphangiogenic processes in vivo. EC spheroids can also be coimplanted with other cell types for tissue engineering purposes
    Type of Publication: Journal article published
    PubMed ID: 18391960
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  • 7
    Keywords: CANCER ; EXPRESSION ; BLOOD ; Germany ; THERAPY ; INFORMATION ; RISK ; TIME ; PATIENT ; RISK-FACTORS ; CARCINOGENESIS ; ASSOCIATION ; BREAST ; breast cancer ; BREAST-CANCER ; WOMEN ; risk factors ; cancer risk ; DIETARY ; case-control studies ; CALCIUM ; DIETARY-INTAKE ; CELL-GROWTH ; SERUM ; ONCOLOGY ; case-control study ; REGRESSION ; RE ; THERAPIES ; ESTROGEN ; analysis ; RISK-FACTOR ; CANCER-RISK ; ENGLAND ; VITAMIN-D-RECEPTOR ; VITAMIN-D ; postmenopausal ; PERSONAL INTERVIEW ; D METABOLITES ; 1,25-DIHYDROXYVITAMIN-D RECEPTORS ; D DEFICIENCY ; HYPOVITAMINOSIS-D
    Abstract: Various studies suggest that vitamin D may reduce breast cancer risk. Most studies assessed the effects of dietary intake only, although endogenous production is an important source of vitamin D. Therefore, the measurement of serum 25-hydroxyvitamin D [25(OH)D] better indicates overall vitamin D status. To assess the association of 25(OH)D serum concentrations with post-menopausal breast cancer risk, we used a population-based case-control study in Germany, which recruited incident breast cancer patients aged 50-74 between 2002 and 2005. Information on sociodemographic and breast cancer risk factors was collected by personal interview. For this analysis, we included 1394 cases and 1365 controls, matched on year of birth and time of blood collection. Conditional logistic regression was used to calculate odds ratios (ORs) for breast cancer adjusted for potential confounders. Serum 25(OH)D concentration was significantly inversely associated with post-menopausal breast cancer risk. Compared with the lowest category (〈 30 nM), OR [95% confidence intervals (CI)] for the higher categories of 25(OH)D (30-45, 45-60, 60-75 and 〉= 75 nM) were 0.57 (0.45-0.73), 0.49 (0.38-0.64), 0.43 (0.32-0.57) and 0.31 (0.24-0.42), respectively (P-trend 〈 0.0001). Analysis using fractional polynomials indicated a non-linear association. The association was stronger in women never using menopausal hormone therapy (HT) compared with past and current users (P-interaction 〈 0.0001). Our findings strongly suggest a protective effect for post-menopausal breast cancer through a better vitamin D supply as characterized by serum 25(OH)D measurement, with a stronger inverse association in women with low serum 25(OH)D concentrations (〈 50 nM)
    Type of Publication: Journal article published
    PubMed ID: 17974532
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  • 8
    Keywords: APOPTOSIS ; CELLS ; GROWTH ; IN-VITRO ; tumor ; BLOOD ; CELL ; Germany ; human ; IN-VIVO ; tumor growth ; VITRO ; GENE-EXPRESSION ; ACTIVATION ; MECHANISM ; mechanisms ; T cell ; T cells ; T-CELL ; T-CELLS ; NO ; MEMBRANE ; leukemia ; LYMPHOCYTES ; T-LYMPHOCYTES ; T lymphocyte ; ENDOPLASMIC-RETICULUM ; ANTICANCER DRUGS ; T lymphocytes ; signaling ; RE ; XENOGRAFTS ; TUMOR-GROWTH ; HYDROGEN-PEROXIDE ; USA ; HEPATOCELLULAR-CARCINOMA CELLS ; MEDICINE ; MITOCHONDRIAL PERMEABILITY TRANSITION ; PHOSPHOLIPASE C-GAMMA-1 ; CA2+ MOBILIZATION ; CYCLOPHILIN-D ; SCUTELLARIA-BAICALENSIS GEORGI
    Abstract: Herbs have successfully been used in traditional Chinese medicine for centuries. However, their curative mechanisms remain largely unknown. In this study, we show that Wogonin, derived from the traditional Chinese medicine Huang-Qin (Scutellaria baicalensis Georgi), induces apoptosis in malignant T cells in vitro and suppresses growth of human T-cell leukemia xenografts in vivo. Importantly, Wogonin shows almost no toxicity on T lymphocytes from healthy donors. Wogonin induces prolonged activation of PLC gamma 1 via H2O2 signaling in malignant T cells, which leads to sustained elevation of cytosolic Ca2+ in malignant but not normal T cells. Subsequently, a Ca2+ overload leads to disruption of the mitochondrial membrane. The selective effect of Wogonin is due to its differential regulation of the redox status of malignant versus normal T cells. In addition, we show that the L-type voltage-dependent Ca2+ channels are involved in the intracellular Ca2+ mobilization in T cells. Furthermore, we show that malignant T cells possess elevated amounts of voltage-dependent Ca2+ channels compared with normal T cells, which further enhance the cytotoxicity of Wogonin for malignant T cells. Taken together, our data show a therapeutic potential of Wogonin for the treatment of hematologic malignancies
    Type of Publication: Journal article published
    PubMed ID: 18070986
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  • 9
    Keywords: Germany ; DIAGNOSIS ; FOLLOW-UP ; imaging ; INFORMATION ; SUPPORT ; SYSTEM ; SYSTEMS ; TISSUE ; SURGERY ; TARGET ; RADIOFREQUENCY ABLATION ; TARGETS ; TRENDS ; ORDER ; RE ; RADICAL PROSTATECTOMY ; TECHNICAL ASPECTS ; TECHNOLOGY ; liver surgery ; USA ; RESPIRATORY MOTION ; image-guided surgery ; navigation ; AUGMENTED-REALITY ; CHALLENGES ; BEATING HEART-SURGERY ; INTERVENTIONS ; LAPAROSCOPIC ULTRASOUND NAVIGATION ; MINIMALLY INVASIVE SURGERY
    Abstract: Despite rapid developments in the research areas of medical imaging, medical image processing, and robotics, the use of computer assistance in surgical routine is still limited to diagnostics, surgical planning, and interventions on mostly rigid structures. In order to establish a computer-aided workflow from diagnosis to surgical treatment and follow-up, several proposals for computer-assisted soft tissue interventions have been made in recent years. By means of different pre- and intraoperative information sources, such as surgical planning, intraoperative imaging, and tracking devices, surgical navigation systems aim to support surgeons in localizing anatomical targets, observing critical structures, and sparing healthy tissue. Current research in particular addresses the problem of organ shift and tissue deformation, and obstacles in communication between navigation system and surgeon. In this paper, we review computer-assisted navigation systems for soft tissue surgery. We concentrate on approaches that can be applied in endoscopic thoracic and abdominal surgery, because endoscopic surgery has special needs for image guidance due to limitations in perception. Furthermore, this paper informs the reader about new trends and technologies in the area of computer-assisted surgery. Finally, a balancing of the key challenges and possible benefits of endoscopic navigation refines the perspectives of this increasingly important discipline of computer-aided medical procedures
    Type of Publication: Journal article published
    PubMed ID: 18366319
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  • 10
    Keywords: CANCER ; CELLS ; EXPRESSION ; IN-VITRO ; tumor ; CELL ; Germany ; human ; KINASE ; PATHWAY ; PATHWAYS ; VITRO ; GENE ; GENE-EXPRESSION ; PROTEIN ; PROTEINS ; TUMORS ; MESSENGER-RNA ; ANTIGEN ; SKIN ; BIOLOGY ; PROTEIN-KINASE ; ACID ; NO ; gene expression ; PROMOTER ; MELANOMA ; RETINOIC ACID ; signaling ; ONCOLOGY ; recoverin ; RE ; LIGHT ; MELANOMA-CELLS ; LEVEL ; USA ; cancer research ; photoreceptor proteins ; RAT RETINA ; DARK CYCLE ; DIURNAL EXPRESSION ; OPSIN ; RETINOBLASTOMA CELLS
    Abstract: Proteins involved in the visual signaling cascade show light-dependent expression levels in photoreceptor cells. Recently, these proteins have been described to be expressed in neuroectodermal tumors and to function as cancer-retina antigens. Here, we show that light can down-regulate gene expression of rhodopsin, transducin, and cyclic guanosine 3',5'-monophosphate phosphodiesterase 6 (PDE6) and up-regulate guanylyl cyclase 1, recoverin, and arrestin in human melanoma cells in vitro, comparable to physiologic changes earlier observed in photoreceptor cells. Similar modulation can be detected at the protein level in melanoma cells except for no changes in PDE6 protein levels. Two regulatory pathways have been identified: Sp1/Sp3/Sp4 proteins for rhodopsin and PDE6, and mitogen-activated protein kinases for recoverin and arrestin. The visual cascade and retinoic acid as its derivate do not play any role in this process. Putative explanations for light-dependent modulation of cancer-retina antigen expression in melanoma cells are discussed
    Type of Publication: Journal article published
    PubMed ID: 18184973
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  • 11
    Keywords: RECEPTOR ; CELL ; Germany ; MODEL ; DENSITY ; VOLUME ; GENE ; TRANSDUCTION ; ACTIVATION ; COMPLEX ; RESPONSES ; COMPLEXES ; DOMAIN ; BIOLOGY ; MOLECULAR-BIOLOGY ; signal transduction ; SIGNAL ; MUTANT ; AMPLIFICATION ; SIGNAL-TRANSDUCTION ; EFFICIENT ; LOCALIZATION ; PROGENITOR CELLS ; CELL-SURFACE ; point mutation ; DIMERIZATION ; DOMAINS ; ERYTHROPOIETIN ; ERYTHROPOIETIN RECEPTOR ; LAYER ; OLIGOMERIZATION ; signaling ; molecular biology ; molecular ; RE ; VARIANT ; RESPONSIVENESS ; analysis ; MUTANTS ; TRANSMEMBRANE DOMAIN ; USA ; correlation ; SET ; NOV ; correlates ; modeling ; response ; erythrocytosis ; FUNCTIONALITY ; biological ; MEMBRANE-PROTEINS ; PRIMARY FAMILIAL POLYCYTHEMIA
    Abstract: The formation of signal-promoting dimeric or oligomeric receptor complexes at the cell surface is modulated by self-interaction of their transmembrane (TM) domains. To address the importance of TM domain packing density for receptor functionality, we examined a set of asparagine mutants in the TM domain of the erythropoietin receptor (EpoR). We identified EpoR-T242N as a receptor variant that is present at the cell surface similar to wild-type EpoR but lacks visible localization in vesicle-like structures and is impaired in efficient activation of specific signaling cascades. Analysis by a molecular modeling approach indicated an increased interhelical distance for the EpoR-T242N TM dimer. By employing the model, we designed additional mutants with increased or decreased packing volume and confirmed a correlation between packing volume and biological responsiveness. These results propose that the packing density of the TM domain provides a novel layer for fine-tuned regulation of signal transduction and cellular decisions
    Type of Publication: Journal article published
    PubMed ID: 18855427
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  • 12
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    Human Heredity 66 (3), 170-179 
    Keywords: ENVIRONMENT ; CANCER ; Germany ; LUNG ; MODEL ; MODELS ; lung cancer ; LUNG-CANCER ; DISEASE ; DISEASES ; EPIDEMIOLOGY ; EXPOSURE ; RISK ; RISKS ; GENE ; GENES ; COMPONENTS ; COMPLEX ; ASSOCIATION ; SUSCEPTIBILITY ; VARIANTS ; IDENTIFICATION ; lifestyle ; NUMBER ; genetics ; CIGARETTE-SMOKING ; etiology ; smoking ; PARAMETERS ; gene-environment interaction ; INDIVIDUALS ; PREVALENCE ; BEHAVIOR ; CONSUMPTION ; heredity ; RELATIVE RISK ; RE ; DEPENDENCE ; methods ; GENOTYPE ; RISK-FACTOR ; EXTENT ; ENVIRONMENTAL-FACTORS ; interactions ; EXCESS ; familial relative risk ; genotype relative risk ; NEWLY MARRIED-COUPLES ; SMOKING-CESSATION
    Abstract: Objectives: Parents share genes and environmental exposures with their offspring. Spouses are often unrelated and their excess of genetic sharing is low, but the similar lifestyles of spouses regarding, for example, tobacco consumption may also result in a familial clustering of disease. This study investigates the influence of gene-environment interactions on the relative risks of disease for the offspring and the spouses of affected individuals. Methods: Theoretical models were developed to explore the dependence of familial relative risks on environmental parameters (exposure frequency, relative risk of disease for exposed versus unexposed individuals, extent of environmental sharing), on genetic parameters (allele frequency, genotype relative risk and mode of inheritance), on the number of descendants in exposed versus unexposed individuals, and on the model of gene-environment interaction. Lung cancer was used as an example of a complex disease with smoking as a known risk factor. Results: The parent-offspring and the spouse-spouse relative risks of disease varied widely in the strength of the environmental and genetic components and their degree of interaction. The familial relative risk of lung cancer decreased with increasing smoking prevalence. The relationship between exposure frequency and relative risk was markedly different when genes and environment had similar effects on disease susceptibility. Conclusions: Estimates of the relative risk of disease for varying exposure frequencies may help to assess the relevance of genetic effects in disease etiology. In particular, a positive association between offspring relative risk and exposure frequency may be indicative of genes interacting with environmental factors of similar effect sizes, with the corresponding implications for gene identification studies. Copyright (C) 2008 S. Karger AG, Basel
    Type of Publication: Journal article published
    PubMed ID: 18493142
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  • 13
    Keywords: CELL ; Germany ; INHIBITION ; KINASE ; SUPPORT ; GENE ; PROTEIN ; RNA ; transcription ; COMPONENTS ; RELEASE ; COMPLEX ; MECHANISM ; BINDING ; BIOLOGY ; cell cycle ; CELL-CYCLE ; MOLECULAR-BIOLOGY ; PHOSPHORYLATION ; PROTEIN-KINASE ; CHROMATIN ; SUBUNITS ; FLUORESCENCE ; INITIATION ; molecular biology ; molecular ; RE ; FACTOR TIF-IA ; GENE-TRANSCRIPTION ; nucleolus ; RNA polymerase I ; PHASE ; USA ; HUMAN-CELLS ; microbiology ; CASEIN KINASE-II ; RDNA TRANSCRIPTION ; FLUORESCENCE RECOVERY ; GROWTH-CONTROL ; CELL BIOLOGY ; cell cycle arrest ; DNA-TRANSCRIPTION
    Abstract: The protein kinase casein kinase 2 (CK2) phosphorylates different components of the RNA pollymerase I (Poll 1) transcription machinery and exerts a positive effect on rRNA gene (rDNA) transcription. Here we show that CK2 phosphorylates the transcription initiation factor TIF-IA at serines 170 and 172 (Ser170/172), and this phosphorylation triggers the release of TIF-IA from Poll I after transcription initiation. Inhibition of Ser170/172 phosphorylation or covalent tethering of TIF-IA to the RPA43 subunit of Pol I inhibits rDNA transcription, leading to perturbation of nucleolar structure and cell cycle arrest. Fluorescence recovery after photobleaching and chromatin immunoprecipitation experiments demonstrate that dissociation of TIF-IA from Pol I is a prerequisite for proper transcription elongation. In support of phosphorylation of TIF-IA switching from the initiation into the elongation phase, dephosphorylation of Ser170/172 by FCP1 facilitates the reassociation of TIF-IA with Pol I, allowing a new round of rDNA transcription. The results reveal a mechanism by which the functional interplay between CK2 and FCP1 sustains multiple rounds of Pol I transcription
    Type of Publication: Journal article published
    PubMed ID: 18559419
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  • 14
    Keywords: RECEPTOR ; proliferation ; CELL ; Germany ; PATHWAY ; liver ; GENE ; GENES ; PROTEIN ; PROTEINS ; transcription ; MICE ; TRANSCRIPTION FACTOR ; hepatocytes ; cell cycle ; CELL-CYCLE ; TARGET ; MUTANT ; PROGRESSION ; PROMOTER ; MITOSIS ; INJURY ; ADULT ; RE ; ASSEMBLIES ; assembly ; MOUSE-LIVER ; USA ; regeneration ; PROGRAMS ; NUCLEAR RECEPTOR ; DRUG-METABOLISM ; CELL-SIZE ; EFFECTORS ; PROLIFERATIVE RESPONSE
    Abstract: In the adult liver, 1,4-bis[2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP), an agonist of the constitutive androstane receptor (CAR, NR1I3), produces rapid hepatomegaly in the absence of injury. In this study, we identify c-Myc as a gene induced by CAR and demonstrate that TCPOBOP-induced proliferation of hepatocytes depends on c-Myc function. Moreover, the TCPOBOP-induced cell cycle program (Cdc2, cyclins, MCM proteins, Cdc20, and genes implicated in the spindle assembly checkpoint) is severely impaired in c-Myc mutant livers. Strikingly, many of these genes overlap with a program controlled by the forkhead transcription factor FoxM1, known to control progression through S-phase and mitosis. Indeed, FoxM1 is also induced by TCPOBOP. Moreover, we show that c-Myc binds to the FoxM1 promoter in a TCPOBOP-dependent manner, suggesting a CAR -〉 c-Myc -〉 FoxM1 pathway downstream of TCPOBOP. Conclusion: Collectively, this study identifies c-Myc and FoxM1 mediated proliferative programs as key mediators of TCPOBOP-CAR induced direct liver hyperplasia
    Type of Publication: Journal article published
    PubMed ID: 18798339
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  • 15
    Keywords: CANCER ; Germany ; screening ; EPIDEMIOLOGY ; incidence ; MORTALITY ; prevention ; AGE ; WOMEN ; colorectal cancer ; MEN ; COLORECTAL-CANCER ; COUNTRIES ; GUIDELINES ; ONCOLOGY ; RE ; aging ; LEVEL ; ENGLAND
    Abstract: We assessed incidence and mortality of colorectal cancer (CRC) at various ages among women and men in 38 European countries. The ages at which defined levels of incidence and mortality were reached varied between 9 and 17 years between countries. This variation requires consideration in the definition of screening guidelines
    Type of Publication: Journal article published
    PubMed ID: 18628760
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  • 16
    Keywords: CANCER ; Germany ; incidence ; REDUCTION ; LESIONS ; colorectal cancer ; COLORECTAL-CANCER ; COST-EFFECTIVENESS ; SURVEILLANCE ; RANDOMIZED-TRIAL ; RE ; ELDERLY-PATIENTS ; colonoscopy ; methods ; CANCERS ; FLEXIBLE SIGMOIDOSCOPY ; SERVICES TASK-FORCE ; POLYPECTOMY ; BASE-LINE FINDINGS
    Abstract: Epidemiological evidence suggests that incidence of colorectal cancer can be reduced by 60-90% among participants of preventive colonoscopy with removal of precancerous lesions. Even with sigmoidosopy, the majority of cancers can be prevented. Cost-effectiveness analyses suggest screening schemes based on colonoscopy every 10 years or on sigmoidoscopy every 5 years to be highly cost effective compared to other preventive measures. Even higher cost-effectiveness is to be expected if screening intervals can be extended to 20 or more years, as suggested by recent epidemiological evidence
    Type of Publication: Journal article published
    PubMed ID: 18368634
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  • 17
    Keywords: SURVIVAL ; BLOOD ; CELL ; Germany ; THERAPY ; DIAGNOSIS ; EPIDEMIOLOGY ; LONG-TERM ; TIME ; PATIENT ; prognosis ; TRANSPLANTATION ; CONTRAST ; NO ; AGE ; leukemia ; DATABASE ; SURVEILLANCE ; UNITED-STATES ; NATURAL-HISTORY ; TRENDS ; STATES ; RE ; INCREASE ; PERIOD ANALYSIS ; fludarabine ; rituximab ; analysis ; cancer registry ; USA ; EMPIRICAL-EVALUATION ; STEM ; INCREASES ; UP-TO-DATE
    Abstract: Although chronic lymphocytic leukemia (CLL) has remained incurable with standard treatments, newer therapeutic approaches, such as chemoimmunotherapy or stem cell transplantation, bear the potential for prolonged survival. We estimated trends in age-specific 5- and 10-year absolute and relative survival of CLL patients in the United States between 1980-1984 and 2000-2004 from the 1973 to 2004 database of the Surveillance, Epidemiology, and End Results Program. Period analysis was used to disclose recent developments with minimum delay. Overall, 5- and 10-year absolute survival from diagnosis increased from 54.2% to 60.2% (+6 percentage points; P 〈 .0001) and from 27.8% to 34.8% (+7 percentage points; P 〈 .0001), respectively. Despite a strong age gradient in prognosis, increases in 5-year absolute and relative survival over time were rather homogeneous across age groups. In contrast, increases in 10-year absolute and relative survival close to or well above 10% units were observed for all patients younger than 80 years of age at diagnosis compared with no increase at all for older patients. Long-term survival expectations of patients with CLL have substantially improved over the past 2 decades except for patients 80 years of age or older at the time of diagnosis. Future studies are needed to confirm and expand our findings
    Type of Publication: Journal article published
    PubMed ID: 18309034
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  • 18
    Keywords: INHIBITOR ; SURVIVAL ; CELL ; Germany ; KINASE ; THERAPY ; TYROSINE KINASE ; DIAGNOSIS ; EPIDEMIOLOGY ; LONG-TERM ; POPULATION ; PATIENT ; IMPACT ; TRANSPLANTATION ; BASE ; TYROSINE KINASE INHIBITOR ; AGE ; leukemia ; LONG-TERM SURVIVAL ; SURVEILLANCE ; UNITED-STATES ; CHRONIC MYELOGENOUS LEUKEMIA ; CHRONIC MYELOID-LEUKEMIA ; imatinib ; TRENDS ; STATES ; FINLAND ; REGISTRY ; RE ; THERAPIES ; aging ; cancer registries ; INCREASE ; PERIOD ANALYSIS ; IMATINIB MESYLATE ; LEVEL ; analysis ; KINASE INHIBITOR ; EMPIRICAL-EVALUATION ; IMPROVEMENT ; STEM ; cancer survival ; UP-TO-DATE ; RECORDS ; HEMATOPOIETIC STEM ; CLINICAL-PRACTICE ; chronic myelocytic leukemia
    Abstract: Within the past decades, major advances in therapy for chronic myelocytic leukemia, including allogeneic hematopoietic stem cell transplantation, interferon therapy, and, more recently, also therapy with the tyrosine kinase inhibitor imatinib, have entered clinical practice. The impact of these advances on long-term survival on the population level should be disclosed as timely as possible. We estimated trends in age specific 5- and 10-year relative survival of chronic myelocytic leukemia patients in the United States from 1990-1992 to 2002-2004. Our analysis is based on records from 8,329 patients aged 15 years or older with a first diagnosis of chronic myelocytic leukemia included in the 1973-2004 data base of the Surveillance, Epidemiology, and End Results Program. Period analysis was used to disclose recent developments with minimum delay. Overall, 5-year relative survival increased from 27 to 49%, and 10-year relative survival increased from 9.5 to 34% between 1990-92 and 2002-04. The increase was most dramatic for younger patients, with 10-year relative survival increasing from 16 to 72% in age group 15-44 years, from 12 to 54% in age group 45-54 years, and from 8 to 34% in age group 55-64 years (p〈0.0001 in all cases). Improvements were more modest and not statistically significant, and survival remained at much lower levels among age groups 65-74 and 75+ years. Our analysis discloses a dramatic recent increase in long-term survival of younger patients with chronic myelocytic leukemia which most likely reflects rapid dissemination of advances in therapy on the population level
    Type of Publication: Journal article published
    PubMed ID: 18641022
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  • 19
    Keywords: CANCER ; SURVIVAL ; Germany ; neoplasms ; COHORT ; DISTINCT ; PATIENT ; prognosis ; PERFORMANCE ; EXPERIENCE ; DIFFERENCE ; LONG-TERM SURVIVAL ; STRATEGIES ; PREDICTION ; TRENDS ; FINLAND ; ONCOLOGY ; REGISTRY ; RE ; aging ; cancer registries ; INCREASE ; PATIENT SURVIVAL ; PERIOD ANALYSIS ; analysis ; cancer registry ; USA ; statistical methods ; cohort analysis ; CANCERS ; population-based ; EMPIRICAL-EVALUATION ; PREDICT ; cancer survival ; UP-TO-DATE ; modeling ; ERRORS
    Abstract: Recently, 2 modeling strategies have been proposed and shown to be useful to increase precision of up-to-date cancer survival estimates and to predict cancer patient survival: modeled period analysis and modeled cohort analysis. We aimed to compare the performance of both types of modeling for providing up-to-date and precise cancer survival estimates. Data from the nationwide Finnish Cancer Registry were used to assess how well both approaches would have been able to predict 5-year relative survival of concurrently diagnosed patients if they had been applied for that purpose throughout the past decades. Analyses were carried out for 20 common forms of cancer. For each cancer, 5-year relative survival was modeled with either approach for each single calendar year from 1962 to 1997. Mean differences and mean squared differences from 5-year relative survival later observed for patients diagnosed in the 5-year period around those calendar years were calculated. Survival estimates obtained by period modeling had much lower standard errors than those obtained by cohort modeling. Furthermore, for a clear majority of cancers, period modeling on average also provided better prediction of 5-year relative survival than cohort modeling. We conclude that, although both modeling strategies have their merits and specific indications, period modeling of survival has distinct advantages for up-to-date and precise estimation of cancer survival in population-based cancer survival studies. (C) 2007 Wiley-Liss, Inc
    Type of Publication: Journal article published
    PubMed ID: 17957801
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  • 20
    Keywords: CANCER ; Germany ; screening ; HISTORY ; incidence ; POPULATION ; RISK ; PATIENT ; FAMILY ; HEALTH ; DIFFERENCE ; AGE ; family history ; WOMEN ; meta-analysis ; colorectal cancer ; MEN ; COLORECTAL-CANCER ; COLON-CANCER ; UNITED-STATES ; RELATIVES ; INITIATION ; RELATIVE RISK ; GUIDELINES ; STATES ; REGISTRY ; review ; RE ; AGGREGATION ; FAMILIES ; aging ; cancer registries ; colonoscopy ; METAANALYSIS ; LEVEL ; methods ; cancer registry ; FAMILY-HISTORY ; PEOPLE ; RECOMMENDATIONS ; population-based ; ENGLAND ; LARGE-BOWEL-CANCER ; GRADIENT ; STATE
    Abstract: OBJECTIVES: To review and combine the best available epidemiological evidence, by sex and age, that may help decision and policy makers form recommendations as to how much earlier colorectal cancer (CRC) screening should be initiated among people with a family history of CRC than among average-risk people. PATIENTS AND METHODS: Combining population-based cancer registry and health interview survey data from the United States and results of a recent meta-analysis of epidemiological studies, we estimated cumulative incidence of CRC within subsequent 10 yr (Cl-10) at various ages among men and women with and without a family history of CRC. We estimated both the Cl-10 levels reached in average-risk 45-, 50-, 55-, and 60-yr-old men and women and the age at which the same Cl-10 levels are reached in men and women with a history of CRC in a first-degree relative. RESULTS: Despite major differences in CRC risk by sex, and despite the strong age gradient in relative risk associated with a positive family history, "risk advancement periods" for those with a family history were consistently found to be between 9 and 11 yr for both sexes and at all four ages assessed. CONCLUSION: Advancement of first CRC screening by 10 yr among both men and women with a family history of CRC compared to the average-risk population (e.g., from 50 to 40 yr of age) appears to be a reasonable, evidence-based recommendation
    Type of Publication: Journal article published
    PubMed ID: 18702651
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  • 21
    Keywords: CANCER ; Germany ; RISK ; NEOPLASIA ; RE ; colonoscopy ; USA ; MEDICINE
    Type of Publication: Journal article published
    PubMed ID: 19090029
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  • 22
    Keywords: CANCER ; EXPRESSION ; tumor ; COMBINATION ; Germany ; TYROSINE KINASE ; imaging ; screening ; CLONING ; TUMORS ; NUCLEAR-MEDICINE ; LIGAND ; FAMILY ; BASE ; DISCOVERY ; score ; TRIAL ; IDENTIFICATION ; EFFICIENT ; DATABASE ; LIGANDS ; PHARMACOKINETICS ; nuclear medicine ; TRACER ; INHIBITORS ; radiology ; RE ; SOFTWARE ; methods ; NUCLEAR ; 3D ; CRITERIA ; GA-68-DOTATOC ; docking ; SET ; MEDICINE ; modeling ; SOMATOSTATIN RECEPTOR ; IN-SILICO ; SSTR2 ; virtuals screening ; Y-90-DOTATOC THERAPY
    Abstract: New ligands are needed to improve diagnostics and treatment of SSTR2 expressing tumors. We implemented a procedure to identify ligands based on computer processing methods. A multistep procedure was used. Search entries were taken from National Cancer Institute database. Application of criteria defined by the Lipinski rules reduced the initial data set. Then a pharmacophore criterion including Lys and Trp residues was the next step of the hierarchical filtering, and the ligands considered were transformed from 2D to 3D. Finally, dedicated software was applied for docking ligand studies. Our results have shown that by virtual screening and trial docking, we identified novel ligands with better scores of docked poses compared with previously reported ligands. In conclusion, the use of a focused library that incorporates an initial probe, improved the possibility of a successful virtual screening as compared with random screening and is cost efficient by further combination of trial docking
    Type of Publication: Journal article published
    PubMed ID: 18815664
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  • 23
    Keywords: SURVIVAL ; BLOOD ; COMBINATION ; Germany ; DISEASE ; EPIDEMIOLOGY ; LONG-TERM ; POPULATION ; PATIENT ; prognosis ; LYMPHOMA ; AGE ; chemotherapy ; DATABASE ; SURVEILLANCE ; UNITED-STATES ; TRENDS ; STATES ; RE ; ELDERLY-PATIENTS ; INCREASE ; PERIOD ANALYSIS ; LEVEL ; analysis ; USA ; EMPIRICAL-EVALUATION ; INCREASES ; TO-DATE ; CHILDHOOD-CANCER SURVIVOR ; COLLABORATIVE BRITISH COHORT ; COPP-ABVD ; STUDY-GROUP GHSG
    Abstract: Since the breakthroughs in combination chemotherapy of patients with Hodgkin disease (HD) starting in the 1960s, prognosis of patients has been rising steadily. Trends in long-term survival of patients with HD on the population level should therefore be monitored in an as timely as possible manner. We assessed trends in age specific 5- and 10-year relative survival of patients with HD in the United States from 1980-1984 to 2000-2004 from the 1973-2004 database of the Surveillance, Epidemiology, and End Results (SEER) Program. Period analysis was used to disclose recent developments with minimum delay. Overall, 5-year relative survival steadily increased from 73.5% to 85.2% (+11.7 percentage units), and 10-year relative survival increased from 62.1% to 80.1% (+18.0 percentage units) between 1980-1984 and 2000-2004, according to period analysis. The increase was particularly pronounced for patients aged 45 to 59 years and 60 years and older (increases in 10-year relative survival by 24.8 and 23.3 percentage points, respectively). Nevertheless, a strong age gradient persisted, with 10-year relative survival of 92.7%, 88.7%, 84.9%, 76.2%, and 44.9% in patients aged 15 to 24 years, 25 to 34 years, 35 to 44 years, 45 to 54 years, and 60 years and older, respectively, in 2000-2004. Our period analysis discloses ongoing, major improvement in long-term survival of patients with HD in recent years, particularly among older patients
    Type of Publication: Journal article published
    PubMed ID: 18096762
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  • 24
    Keywords: RECEPTOR ; APOPTOSIS ; CELLS ; proliferation ; tumor ; CELL ; Germany ; IN-VIVO ; KINASE ; PATHWAY ; SYSTEM ; DEATH ; NEW-YORK ; NF-KAPPA-B ; ACTIVATION ; MECHANISM ; ANTIGEN ; mechanisms ; T cell ; T cells ; T-CELL ; T-CELLS ; cytokines ; STIMULATION ; CELL-DEATH ; FAS-LIGAND EXPRESSION ; INDUCED APOPTOSIS ; LYMPHOCYTES ; GRANZYME-B ; immune response ; IMMUNE-RESPONSE ; NF-kappa B ; RECEPTORS ; FAMILY MEMBER BIM ; SIGNALING COMPLEX ; signaling ; BODIES ; CYTOKINE ; ONCOLOGY ; review ; RE ; IMMUNE-SYSTEM ; cell death ; ANTIGEN RECEPTORS ; HPK1 ; progenitor ; AICD ; HEMATOPOIETIC PROGENITOR KINASE-1 ; KINASE-C-THETA ; death receptor ; USA ; CASPASE-MEDIATED CLEAVAGE ; ACAD ; LIGATION
    Abstract: Lymphocytes of the adaptive immune system play a crucial role in defending the organism against pathogens. Initial stimulation via antigen receptors induces activation and proliferation of lymphocytes to generate effector cells that clear the pathogen from the body. During the shut-down of the immune response activated lymphocytes are removed by two mechanisms. T cells that are restimulated during the end of the immune response die by activation-induced cell death (AICD), whereas activated lymphocytes which are not restimulated die by activated cell autonomous death (ACAD). Here, we discuss the regulation of AICD and ACAD in T cells and review the role of cytokines, T cell receptor (TCR) proximal signaling mediators like hematopoietic progenitor kinase 1 (HPK1) and the NF-kappa B pathway. We distinguish between AICD dependent on or independent of death receptor ligation, and discuss caspase-independent death of T cells. (C) 2008 Elsevier Ireland Ltd. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 18289867
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  • 25
    Keywords: RECEPTOR ; APOPTOSIS ; CANCER ; CELLS ; EXPRESSION ; proliferation ; SURVIVAL ; carcinoma ; CELL ; CELL-PROLIFERATION ; Germany ; FOLLOW-UP ; RISK ; SITE ; SITES ; GENE ; GENES ; MARKER ; CARCINOGENESIS ; ASSOCIATION ; polymorphism ; POLYMORPHISMS ; single nucleotide polymorphism ; BREAST ; breast cancer ; BREAST-CANCER ; TARGET ; STAGE ; PROGRESSION ; NUMBER ; METASTASIS ; REGION ; GENOTYPES ; REGIONS ; EXTRACELLULAR-MATRIX ; MIGRATION ; INTEGRIN ; PROGNOSTIC VALUE ; MATRIX ; ONCOLOGY ; RE ; TUMOR-SUPPRESSOR ; MAMMARY-GLAND ; SINGLE NUCLEOTIDE POLYMORPHISMS ; SNPs ; GRADE ; cell proliferation ; SINGLE-NUCLEOTIDE POLYMORPHISMS ; INTEGRINS ; PROGNOSTIC MARKER ; GENOTYPE ; single-nucleotide polymorphism ; HIGH-GRADE ; ENGLAND ; MicroRNAs ; outcome ; MICRORNA ; UNTRANSLATED REGION ; hazard ratio ; SWEDISH ; LEU33PRO HOMOZYGOSITY
    Abstract: Integrins control the cell attachment to the extracellular matrix and play an important role in mediating cell proliferation, migration and survival. A number of important cancer-associated integrin genes can be regulated by microRNAs (miRNAs) that bind to their target sites in the 3' untranslated regions. We examined the effect of single-nucleotide polymorphisms (SNPs) in predicted miRNA target sites of six integrin genes (ITGA3, ITGA6, ITGAv, ITGB3, ITGB4 and ITGB5) on breast cancer (BC) risk and clinical outcome. Six SNPs were genotyped in 749 Swedish incident BC cases with detailed clinical data and up to 15 years of follow-up together with 1493 matched controls. We evaluated associations between genotypes and BC risk and clinical tumour characteristics. Survival probabilities were compared between different subgroups. As a novel finding, several SNPs seemed to associate with the hormone receptor status. The strongest association was observed between the A allele of the SNP rs743554 in the ITGB4 gene and oestrogen receptor-negative tumours [odds ratio 2.09, 95% confidence intervals (CIs) 1.19-3.67]. The same SNP was associated with survival. The A allele carriers had a worse survival compared with the wild-type genotype carriers (hazard ratio 2.11, 95% CIs 1.21-3.68). The poor survival was significantly associated with the aggressive tumour characteristics: high grade, lymph node metastasis and high stage. None of the SNPs was significantly associated with BC risk. As the ITGB4 SNP seems to influence tumour aggressiveness and survival, it may have prognostic value in the clinic
    Type of Publication: Journal article published
    PubMed ID: 18550570
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  • 26
    Keywords: RECEPTOR ; Germany ; IN-VIVO ; KINASE ; MODEL ; MODELS ; TYROSINE KINASE ; GENE ; GENE-EXPRESSION ; MICE ; PATIENT ; DOMAIN ; CONTRAST ; BIOLOGY ; MOLECULAR-BIOLOGY ; MATURATION ; STIMULATION ; MOUSE ; MUTANT ; NO ; resistance ; MUTATION ; genetics ; REGION ; REGIONS ; MUTATIONS ; MUSCLE ; PHENOTYPE ; SKELETAL-MUSCLE ; MOUSE MODEL ; REVEALS ; heredity ; ARCHITECTURE ; molecular biology ; molecular ; ADULT ; RE ; PATTERN ; WEIGHT ; DEFECTS ; MUTANTS ; GENOTYPE ; NERVE ; ENGLAND ; NOV ; ACETYLCHOLINE-RECEPTORS ; CONTRACTION ; DOK7 ; INNERVATION ; KINASE DOMAIN ; KINASE MUSK ; SYNAPSE FORMATION
    Abstract: In the muscle-specific tyrosine kinase receptor gene MUSK, a heteroallelic missense and a null mutation were identified in a patient suffering from a congenital myasthenic syndrome (CMS). We generated one mouse line carrying the homozygous missense mutation V789M in musk (musk(V789M/V789M) mice) and a second hemizygous line, resembling the patient genotype, with the V789M mutation on one allele and an allele lacking the kinase domain (musk(V789M/-) mice). We report here that musk(V789M/V789M) mice present no obvious abnormal phenotype regarding weight, muscle function and viability. In contrast, adult musk(V789M/-) mice suffer from severe muscle weakness, exhibit shrinkage of pelvic and scapular regions and hunchback. Musk(V789M/-) diaphragm develops less force upon direct or nerve-induced stimulation. A profound tetanic fade is observed following nerve-evoked muscle contraction, and fatigue resistance is severely impaired upon a train of tetanic nerve stimulations. Electrophysiological measurements indicate that fatigable muscle weakness is due to impaired neurotransmission as observed in a patient suffering from a CMS. The diaphragm of adult musk(V789M/-) mice exhibits pronounced changes in endplate architecture, distribution and innervation pattern. Thus, the missense mutation V789M in MuSK acts as a hypomorphic mutation and leads to insufficiency in MuSK function in musk(V789M/-) mutants. These mutant mice represent valuable models for elucidating the roles of MuSK for synapse formation, maturation and maintenance as well as for studying the pathophysiology of a CMS due to MuSK mutations
    Type of Publication: Journal article published
    PubMed ID: 18718936
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  • 27
    Keywords: ANGIOGENESIS ; CANCER ; CELLS ; ENDOTHELIAL-CELLS ; EXPRESSION ; GROWTH ; IN-VITRO ; proliferation ; tumor ; CELL ; Germany ; human ; PROSTATE ; GENES ; TISSUE ; MARKER ; TISSUES ; ANTIGEN ; fibroblasts ; TARGET ; PROGRESSION ; METASTASIS ; MIGRATION ; STEM-CELLS ; ADIPOSE-TISSUE ; RE ; fibroblast ; stem cells ; analysis ; USA ; CANDIDATE ; STEM ; PERICYTES ; STROMAL FIBROBLASTS
    Abstract: Endosialin (Tem1) has been identified by two independent experimental approaches as an antigen of tumor-associated endothelial cells, and it has been claimed to be the most abundantly expressed tumor endothelial antigen, making it a prime candidate for vascular targeting purposes. Recent experiments have challenged the endothelial expression of endosialin and suggested an expression by activated fibroblasts and pericytes. Thus, clarification of the controversial cellular expression of endosialin is critically important for an understanding of its role during tumor progression and its validation as a potential therapeutic target. We have therefore performed extensive expression profiling analyses of endosialin. The experiments unambiguously demonstrate that endosialin is expressed by tumor-associated myofibroblasts and mural cells and not by endothelial cells. Endosialin expression is barely detectable in normal human tissues with moderate expression only detectable in the stroma of the colon and the prostate. Corresponding cellular experiments confirmed endosialin expression by mesenchymal cells and indicated that it may in fact be a marker of mesenchymal stem cells. Silencing endosialin expression in fibroblasts strongly inhibited migration and proliferation. Collectively, the experiments validate endosialin as a marker of tumor-associated myofibroblasts and tumor vessel-associated mural cells. The data warrant further functional analysis of endosialin during tumor progression and its exploitation as marker of tumor vessel-associated mural cells, expression of which may reflect the non-normalized phenotype of the tumor vasculature
    Type of Publication: Journal article published
    PubMed ID: 18187565
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  • 28
    Keywords: CELLS ; CELL ; Germany ; KINASE ; SITE ; SITES ; GENE ; DOMAIN ; BIOLOGY ; cell cycle ; CELL-CYCLE ; PHOSPHORYLATION ; PROTEIN-KINASE ; ASSOCIATION ; MATURATION ; IDENTIFICATION ; PROGRESSION ; MUTATION ; LOCALIZATION ; MAMMALIAN-CELLS ; S-PHASE ; MITOSIS ; RE ; centrosome duplication ; PHASE ; CYTOKINESIS ; USA ; PREVENTS ; centrosomes ; NOV ; CELL BIOLOGY ; Plk2 ; Plk4 ; polo-box ; spindles
    Abstract: In mammalian cells, the centrosome consists of a pair of centrioles and amorphous pericentriolar material. The centrosome duplicates once per cell cycle. Polo like kinases (Plks) perform crucial functions in cell cycle progression and during mitosis. The polo-like kinase-2, Plk2, is activated near the G(1)/S phase transition, and plays an important role in the reproduction of centrosomes. In this study, we show that the polo-box of Plk2 is required both for association to the centrosome and centriole duplication. Mutation of critical sites in the Plk2 polo-box prevents centrosomal localization and impairs centriole duplication. Plk2 is localized to centrosomes during early G(1) phase where it only associates to the mother centriole and then distributes equally to both mother and daughter centrioles at the onset of S phase. Furthermore, our results imply that Plk2 mediated centriole duplication is dependent on Plk4 function. In addition, we find that siRNA-mediated downregulation of Plk2 leads to the formation of abnormal mitotic spindles confirming that Plk2 may have a function in the reproduction of centrioles
    Type of Publication: Journal article published
    PubMed ID: 19001868
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  • 29
    Keywords: OPTIMIZATION ; CANCER ; radiotherapy ; PROSTATE ; THERAPY ; VOLUME ; NEW-YORK ; EFFICIENCY ; TISSUE ; PATIENT ; TARGET ; NO ; RADIATION-THERAPY ; prostate cancer ; PROSTATE-CANCER ; BEAM ; NORMAL TISSUE ; treatment planning ; IMRT ; FEASIBILITY ; multi-criteria optimization ; RE ; THERAPIES ; intensity ; USA ; VARIABLES ; multiobjective ; LINEAR-PROGRAMMING APPROACH ; mean-tail-dose ; MULTIOBJECTIVE OPTIMIZATION ; prioritization
    Abstract: Treatment planning for intensity modulated radiation therapy (IMRT) is challenging due to both the size of the computational problems (thousands of variables and constraints) and the multi-objective, imprecise nature of the goals. We apply hierarchical programming to IMRT treatment planning. In this formulation, treatment planning goals/objectives are ordered in an absolute hierarchy, and the problem is solved from the top-down such that more important goals are optimized in turn. After each objective is optimized, that objective function is converted into a constraint when optimizing lower-priority objectives. We also demonstrate the usefulness of a linear/quadratic formulation, including the use of mean-tail-dose (mean dose to the hottest fraction of a given structure), to facilitate computational efficiency. In contrast to the conventional use of dose-volume constraints (no more than x% volume of a structure should receive more than y dose), the mean-tail-dose formulation ensures convex feasibility spaces and convex objective functions. To widen the search space without seriously degrading higher priority goals, we allowed higher priority constraints to relax or 'slip' a clinically negligible amount during lower priority iterations. This method was developed and tuned for external beam prostate planning and subsequently tested using a suite of 10 patient datasets. In all cases, good dose distributions were generated without individual plan parameter adjustments. It was found that allowance for a small amount of 'slip,' especially in target dose homogeneity, often resulted in improved normal tissue dose burdens. Compared to the conventional IMRT treatment planning objective function formulation using a weighted linear sum of terms representing very different dosimetric goals, this method: (1) is completely automatic, requiring no user intervention, (2) ensures high-priority planning goals are not seriously degraded by lower-priority goals, and (3) ensures that lower priority, yet still important, normal tissue goals are separately pushed as far as possible without seriously impacting higher priority goals. (C) 2007 Elsevier Inc. All rights reserved
    Type of Publication: Journal article published
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  • 30
    Keywords: CANCER ; LUNG ; DIAGNOSIS ; FOLLOW-UP ; lung cancer ; LUNG-CANCER ; EPIDEMIOLOGY ; incidence ; POPULATION ; RISK ; SITE ; SITES ; PATIENT ; primary ; PATTERNS ; NUMBER ; AGE ; smoking ; RATES ; cancer risk ; REGION ; FRANCE ; SQUAMOUS-CELL CARCINOMA ; HEAD ; ALCOHOL ; PREVALENCE ; TOBACCO SMOKING ; second cancer ; MULTICENTER ; NECK-CANCER ; ONCOLOGY ; REGISTRY ; RE ; PATTERN ; head and neck cancer ; cancer registries ; SURVIVORS ; analysis ; MALIGNANT-TUMORS ; cancer registry ; pooled analysis ; USA ; CANCER INCIDENCE ; CANCERS ; population-based ; CANCER-RISK ; NOV ; ORAL-CAVITY ; ALCOHOL-DRINKING ; EXCESS ; POOLED-ANALYSIS ; second primary ; YOUNG-PATIENTS
    Abstract: The objective of the study was to assess the risk of second primary cancers (SPCs) following a primary head and neck cancer (oral cavity, pharynx and larynx) and the risk of head and neck cancer as a PC. The present investigation is a multicenter study from 13 population-based cancer registries. The study population involved 99,257 patients with a first primary head and neck cancer and contributed 489,855 person-years of follow-up. To assess the excess risk of SPCs following head and neck cancers, we calculated standardized incidence ratios (SIRs) by dividing the observed numbers of SPCs by the expected number of cancers calculated from accumulated person-years and the age, sex- and calendar period-specific first primary cancer incidence rates in each of the cancer registries. During the observation period, there were 10,826 cases of SPCs after head and neck cancer. For all cancer sites combined, the SIR of SPCs was 1.86 (95% CI = 1.83-1.90) and the 20-year cumulative risk was 36%. Lung cancer contributed to the highest proportion of the SPCs with a 20-year cumulative risk of 13%. Excess second head and neck cancer risk was observed 10 years after diagnosis with lymphohaematopoietic cancers. The most common SPC following a first primary head and neck cancer was lung cancer. However, the highest excess of SPCs was in the head and neck region. These patterns were consistent with the notion that the pattern of cancer in survivors of head and neck cancer is dominated by the effect of tobacco smoking and alcohol drinking. (C) 2008 Wiley-Liss, Inc
    Type of Publication: Journal article published
    PubMed ID: 18729183
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  • 31
    Keywords: brain ; RECEPTOR ; CELL ; Germany ; KINASE ; GENE ; PROTEIN ; METABOLISM ; MICE ; TIME ; ACTIVATION ; recombination ; PROTEIN-KINASE ; ALPHA ; hippocampus ; MOUSE ; PLASMA ; FUSION ; inactivation ; PHENOTYPE ; glucocorticoid receptor ; FUSION PROTEIN ; RE ; INCREASE ; RESPONSIVENESS ; FOREBRAIN ; MUTANTS ; BIRTH ; USA ; LOSSES ; ANXIETY ; synthesis ; ADRENAL AXIS
    Abstract: Glucocorticoid action in the brain is mediated by the glucocorticoid receptor (GR) and the mineralocorticoid receptor, thereby affecting physiological processes such as neurogenesis, synaptic plasticity, and neuroendocrine control. To examine GR function in the regulation of the hypothalamic-pituitary-adrenal axis, we generated GR mutant mice that are homozygous for a conditional GR allele and heterozygous for a transgene that expresses the Cre recombinase under control of the regulatory elements of the mouse calcium/calmodulin-dependent protein kinase II alpha gene, resulting in Cre-mediated recombination in the brain and pituitary. The GR mutants die about 1 wk after birth and display a fulminant increase in plasma corticosterone as well as a severe histopathological phenotype. To assess in which time frame targeting of the pituitary occurs during embryonic development, we used a transgenic line expressing an inducible CreER(T2) fusion protein under the control of the regulatory elements of the calcium/ calmodulin-dependent protein kinase II alpha gene. Cre reporter data show that pituitary targeting occurred during embryonic development at the time when glucocorticoid synthesis starts
    Type of Publication: Journal article published
    PubMed ID: 18372328
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  • 32
    Keywords: CELLS ; EXPRESSION ; IN-VITRO ; CELL ; Germany ; human ; IN-VIVO ; VITRO ; VIVO ; DISEASE ; DISEASES ; PROTEIN ; MOLECULES ; MICE ; ACTIVATION ; LIGAND ; RESPONSES ; DNA ; MARKER ; INDUCTION ; ANTIGEN ; DENDRITIC CELLS ; T-CELLS ; papillomavirus ; MOLECULE ; BONE-MARROW ; MATURATION ; MOUSE ; LESIONS ; HUMANS ; MARKERS ; human papillomavirus ; TYPE-16 ; VACCINES ; PARAMETERS ; HUMAN-PAPILLOMAVIRUS ; MHC CLASS-I ;