1,532 results on '"Pantel A"'
Search Results
2. EpCAM-positive circulating tumor cells and serum AFP levels predict outcome after curative resection of hepatocellular carcinoma
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Lorenz Kocheise, Martin Schoenlein, Berit Behrends, Vincent Joerg, Christian Casar, Thorben W. Fruendt, Thomas Renné, Asmus Heumann, Jun Li, Samuel Huber, Ansgar W. Lohse, Klaus Pantel, Sabine Riethdorf, Henning Wege, Kornelius Schulze, and Johann von Felden more...
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Medicine ,Science - Abstract
Abstract Hepatocellular carcinoma (HCC) has high recurrence rates exceeding 50% despite curative resection. The serum biomarker alpha-fetoprotein (AFP) is a well-known prognostic marker for HCC. EpCAM-positive circulating tumor cells (CTC) have a high predictive value for early HCC recurrence after curatively intended resection, most likely indicating micro-metastases at the time of resection. However, sensitivity remains low. The objective of this study was to evaluate a composite test comprising both CTC and AFP to identify patients at high risk for early HCC recurrence. We prospectively enrolled 58 patients undergoing curative intended resection for HCC at a tertiary referral center. Blood specimens were obtained prior to resection and analyzed for EpCAM-positive CTC and serum AFP levels. A positive result was defined as either detection of CTC or AFP levels ≥ 400 ng/ml. Eight patients tested positive for CTC, seven for AFP, and two for both markers. A positive composite test was significantly associated with shorter early recurrence-free survival (5 vs. 16 months, p = 0.005), time to recurrence (5 vs. 16 months, p = 0.011), and overall survival (37 vs. not reached, p = 0.034). Combining CTC and AFP identified patients with poor outcome after surgical resection, for whom adjuvant or neoadjuvant therapies may be particularly desirable. more...
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- 2023
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3. Effectiveness of exercise interventions to improve long-term outcomes in people living with mild cognitive impairment: a systematic review and meta-analysis
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Mirjam Dieckelmann, Ana I. González-González, Winfried Banzer, Andrea Berghold, Klaus Jeitler, Johannes Pantel, Gudrun Pregartner, Arthur Schall, Valentina A. Tesky, and Andrea Siebenhofer
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Medicine ,Science - Abstract
Abstract Although exercise guidelines now recommend exercise for patients with MCI, the long-term effects of exercise in patients with MCI has not been reviewed systematically. The aim was to assess (1) the effectiveness of exercise and physical activity (EXPA) interventions in improving long-term patient-relevant cognitive and non-cognitive outcomes in people with mild cognitive impairment, (2) how well the included trials reported details of the intervention, and (3) the extent to which reported endpoints were in line with patient preferences that were assessed in patient workshops. Following PRISMA guidelines, we performed a systematic review and meta-analysis including randomized controlled trials. A total of ten studies were included after searching in six electronic sources from 1995 onwards. There is a trend that 6 + -month EXPA interventions improve global cognition 12 months after initiation. Evidence on long-term effects of EXPA interventions on non-cognitive health outcomes could not be meaningfully pooled and the individual studies reported mixed results. Workshop participants considered freedom from pain and stress, mood, motivation and self-efficacy to be important, but these outcomes were rarely addressed. Too little information is available on intervention details for EXPA programs to be replicated and confidently recommended for patients with MCI. PROSPERO registration in December, 2021 (CRD42021287166). more...
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- 2023
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4. Early DNase-I therapy delays secondary brain damage after traumatic brain injury in adult mice
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Tobias J. Krämer, Florian Pickart, Bruno Pöttker, Christina Gölz, Axel Neulen, Tobias Pantel, Hermann Goetz, Katharina Ritter, Michael K. E. Schäfer, and Serge C. Thal
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Medicine ,Science - Abstract
Abstract Traumatic brain injury (TBI) causes the release of danger-associated molecular patterns (DAMP) from damaged or dead cells, which contribute to secondary brain damage after TBI. Cell-free DNA (cfDNA) is a DAMP known to cause disruption of the blood–brain barrier (BBB), promote procoagulant processes, brain edema, and neuroinflammation. This study tested the hypothesis that administration of deoxyribonuclease-I (DNase-I) has a beneficial effect after TBI. Mice (n = 84) were subjected to controlled cortical impact (CCI) and posttraumatic intraperitoneal injections of low dose (LD) or high dose (HD) of DNase-I or vehicle solution at 30 min and 12 h after CCI. LD was most effective to reduce lesion volume (p = 0.003), brain water content (p more...
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- 2023
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5. Psychological stress and epigenetic aging in older men: The VA normative aging study
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Jamaji C. Nwanaji-Enwerem, Andres Cardenas, Xu Gao, Cuicui Wang, Pantel Vokonas, Avron Spiro, Anwar D. Osborne, Anna Kosheleva, Lifang Hou, Andrea A. Baccarelli, and Joel Schwartz
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Perceived stress ,DNA methylation ,DNAm age ,Trauma ,Epigenetic clock ,Biological age ,Medicine - Abstract
Psychological stress remains an important risk factor for morbidity and mortality throughout the life course. However, there have been counterintuitive findings reported in previous studies of older persons that examine the relationships of perceived psychological stress with DNA methylation-based markers of aging, which also serve as predictors of morbidity and mortality (epigenetic age/clocks). We aimed to replicate and expand findings from existing work by examining relationships of self-reported stress with nine epigenetic clocks: Hannum, Horvath, Intrinsic, Extrinsic, SkinBloodClock, PhenoAge, GrimAge, DNAm Telomere Length, and Pace of Aging. We analyzed data from 607 male participants (mean age 73.2 years) of the VA Normative Aging Study with one to two study visits from 1999 to 2007 (observations = 956). Stress was assessed via the 14-item Perceived Stress Scale (PSS). Epigenetic age was calculated from DNA methylation measured in leukocytes with the HumanMethylation450 BeadChip. In linear mixed effects models adjusted for demographic/lifestyle/health factors, a standard deviation (sd) increase in PSS was associated with Horvath (β = −0.35-years, 95%CI: −0.61, −0.09, P = 0.008) and Intrinsic (β = −0.40-years, 95%CI: −0.67, −0.13, P = 0.004) epigenetic age deceleration. However, in models limited to participants with the highest levels of stress (≥75th-percentile), Horvath (β = 2.29-years, 95%CI: 0.16, 4.41, P = 0.04) and Intrinsic (β = 2.06-years, 95%CI: −0.17, 4.28, P = 0.07) age acceleration associations were observed. Our results reinforce the complexity of psychological stress and epigenetic aging relationships and lay a foundation for future studies that explore longitudinal relationships with other adult stress metrics and factors that can influence stress such as resilience measures. more...
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- 2023
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6. Ribonuclease-1 treatment after traumatic brain injury preserves blood–brain barrier integrity and delays secondary brain damage in mice
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Tobias J. Krämer, Per Hübener, Bruno Pöttker, Christina Gölz, Axel Neulen, Tobias Pantel, Hermann Goetz, Katharina Ritter, Michael K. E. Schäfer, and Serge C. Thal
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Medicine ,Science - Abstract
Abstract Traumatic brain injury (TBI) involves primary mechanical damage and delayed secondary damage caused by vascular dysfunction and neuroinflammation. Intracellular components released into the parenchyma and systemic circulation, termed danger-associated molecular patterns (DAMPs), are major drivers of vascular dysfunction and neuroinflammation. These DAMPs include cell-free RNAs (cfRNAs), which damage the blood–brain barrier (BBB), thereby promoting edema, procoagulatory processes, and infiltration of inflammatory cells. We tested the hypothesis that intraperitoneal injection of Ribonuclease-1 (RNase1, two doses of 20, 60, or 180 µg/kg) at 30 min and 12 h after controlled-cortical-impact (CCI) can reduce secondary lesion expansion compared to vehicle treatment 24 h and 120 h post-CCI. The lowest total dose (40 µg/kg) was most effective at reducing lesion volume (− 31% RNase 40 µg/kg vs. vehicle), brain water accumulation (− 5.5%), and loss of BBB integrity (− 21.6%) at 24 h post-CCI. RNase1 also reduced perilesional leukocyte recruitment (− 53.3%) and microglial activation (− 18.3%) at 120 h post-CCI, but there was no difference in lesion volume at this time and no functional benefit. Treatment with RNase1 in the early phase following TBI stabilizes the BBB and impedes leukocyte immigration, thereby suppressing neuroinflammation. RNase1-treatment may be a novel approach to delay brain injury to extend the window for treatment opportunities after TBI. more...
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- 2022
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7. P196: GestaltMatcher Database: A FAIR database for medical imaging data of rare diseases
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Hellen Lesmann, Shahida Moosa, Tori Pantel, Stanislav Rosnev, Alexander Hustinx, Behnam Javanmardi, Alexej Knaus, Tom Kamphans, Wolfgang Meiswinkel, Jing-Mei Li, Merle ten Hagen, Pilar Caro, Clara Velmans, Matthias Höller, Ibrahim Abdelrazek, Gehad Elmakkawy, Khoushoua Alaadin, Kimberly Christine Coetzer, Frédéric Ebstein, Sebastian Küry, Ebtesam Abdalla, Miriam Elbracht, Cordula Knopp, Annabelle Arlt, Claudio Graziano, Borovikov Artem, Annette Uwineza, Felix Marbach, Christian Netzer, Rami Abou Jamra, Markus Nöthen, Gholson Lyon, Peter Krawitz, and Tzung-Chien Hsieh more...
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Genetics ,QH426-470 ,Medicine - Published
- 2023
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8. Effectiveness of exercise and physical activity interventions to improve long-term patient-relevant cognitive and non-cognitive outcomes in people living with mild cognitive impairment: a protocol of a systematic review and meta-analysis
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Mirjam Dieckelmann, Klaus Jeitler, Andrea Siebenhofer, Ana Isabel González-González, Andrea Berghold, Winfried Banzer, Johannes Pantel, Arthur Schall, and Valentina A Tesky
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Medicine - Abstract
Introduction Mild cognitive impairment (MCI) is a clinical syndrome characterised by persistent cognitive deficits that do not yet fulfil the criteria of dementia. Delaying the onset of dementia using secondary preventive measures such as physical activity and exercise can be a safe way of reducing the risk of further cognitive decline and maintaining independence and improving quality of life. The aim is to systematically review the literature to assess the effectiveness of physical activity and exercise interventions to improve long-term patient-relevant cognitive and non-cognitive outcomes in people living with MCI, including meta-analyses if applicable.Methods and analysis We will systematically search five electronic databases from 1995 onward to identify trials reporting on the effectiveness of physical activity and exercise interventions to improve long-term (12+ months) patient-relevant cognitive and non-cognitive outcomes in adults (50+ years) with MCI. Screening procedures, selection of eligible full-texts, data extraction and risk of bias assessment will be performed in dual-review mode. Additionally, the reporting quality of the exercise interventions will be assessed using the Consensus on Exercise Reporting Template. A quantitative synthesis will only be conducted if studies are homogeneous enough for effect sizes to be pooled. Where quantitative analysis is not applicable, data will be represented in a tabular form and synthesised narratively. People living with MCI will be involved in defining outcome measures most relevant to them in order to assess in how far randomised controlled trials report endpoints that matter to those concerned.Ethics and dissemination Results will be disseminated to both scientific and lay audiences by creating a patient-friendly video abstract. This work will inform professionals in primary care about the effectiveness of physical activity and exercise interventions and support them to make evidence-based exercise recommendations for the secondary prevention of dementia in people living with MCI. No ethical approval required.PROSPERO registration number CRD42021287166. more...
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- 2022
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9. The role of solar and geomagnetic activity in endothelial activation and inflammation in the NAS cohort.
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Jessica E Schiff, Carolina L Z Vieira, Eric Garshick, Veronica Wang, Annelise Blomberg, Diane R Gold, Joel Schwartz, Samantha M Tracy, Pantel Vokonas, and Petros Koutrakis
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Medicine ,Science - Abstract
This study investigated the associations between solar and geomagnetic activity and circulating biomarkers of systemic inflammation and endothelial activation in the Normative Aging Study (NAS) cohort. Mixed effects models with moving day averages from day 0 to day 28 were used to study the associations between solar activity (sunspot number (SSN), interplanetary magnetic field (IMF)), geomagnetic activity (planetary K index (Kp index), and various inflammatory and endothelial markers. Biomarkers included intracellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), C-reactive protein (CRP), and fibrinogen. After adjusting for demographic and meteorological variables, we observed significant positive associations between sICAM-1 and sVCAM-1 concentrations and solar and geomagnetic activity parameters: IMF, SSN, and Kp. Additionally, a negative association was observed between fibrinogen and Kp index and a positive association was observed for CRP and SSN. These results demonstrate that solar and geomagnetic activity might be upregulating endothelial activation and inflammation. more...
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- 2022
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10. DunedinPACE, a DNA methylation biomarker of the pace of aging
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Daniel W Belsky, Avshalom Caspi, David L Corcoran, Karen Sugden, Richie Poulton, Louise Arseneault, Andrea Baccarelli, Kartik Chamarti, Xu Gao, Eilis Hannon, Hona Lee Harrington, Renate Houts, Meeraj Kothari, Dayoon Kwon, Jonathan Mill, Joel Schwartz, Pantel Vokonas, Cuicui Wang, Benjamin S Williams, and Terrie E Moffitt more...
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aging ,geroscience ,biological aging ,gerontology ,DNA methylation ,epigenetic ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
Background: Measures to quantify changes in the pace of biological aging in response to intervention are needed to evaluate geroprotective interventions for humans. Previously, we showed that quantification of the pace of biological aging from a DNA-methylation blood test was possible (Belsky et al., 2020). Here, we report a next-generation DNA-methylation biomarker of Pace of Aging, DunedinPACE (for Pace of Aging Calculated from the Epigenome). Methods: We used data from the Dunedin Study 1972–1973 birth cohort tracking within-individual decline in 19 indicators of organ-system integrity across four time points spanning two decades to model Pace of Aging. We distilled this two-decade Pace of Aging into a single-time-point DNA-methylation blood-test using elastic-net regression and a DNA-methylation dataset restricted to exclude probes with low test-retest reliability. We evaluated the resulting measure, named DunedinPACE, in five additional datasets. Results: DunedinPACE showed high test-retest reliability, was associated with morbidity, disability, and mortality, and indicated faster aging in young adults with childhood adversity. DunedinPACE effect-sizes were similar to GrimAge Clock effect-sizes. In analysis of incident morbidity, disability, and mortality, DunedinPACE and added incremental prediction beyond GrimAge. Conclusions: DunedinPACE is a novel blood biomarker of the pace of aging for gerontology and geroscience. Funding: This research was supported by US-National Institute on Aging grants AG032282, AG061378, AG066887, and UK Medical Research Council grant MR/P005918/1. more...
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- 2022
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11. Quantification of the pace of biological aging in humans through a blood test, the DunedinPoAm DNA methylation algorithm
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Daniel W Belsky, Avshalom Caspi, Louise Arseneault, Andrea Baccarelli, David L Corcoran, Xu Gao, Eiliss Hannon, Hona Lee Harrington, Line JH Rasmussen, Renate Houts, Kim Huffman, William E Kraus, Dayoon Kwon, Jonathan Mill, Carl F Pieper, Joseph A Prinz, Richie Poulton, Joel Schwartz, Karen Sugden, Pantel Vokonas, Benjamin S Williams, and Terrie E Moffitt more...
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aging ,biological aging ,DNA methylation ,epigenetic ,human ,life-course ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
Biological aging is the gradual, progressive decline in system integrity that occurs with advancing chronological age, causing morbidity and disability. Measurements of the pace of aging are needed as surrogate endpoints in trials of therapies designed to prevent disease by slowing biological aging. We report a blood-DNA-methylation measure that is sensitive to variation in pace of biological aging among individuals born the same year. We first modeled change-over-time in 18 biomarkers tracking organ-system integrity across 12 years of follow-up in n = 954 members of the Dunedin Study born in 1972–1973. Rates of change in each biomarker over ages 26–38 years were composited to form a measure of aging-related decline, termed Pace-of-Aging. Elastic-net regression was used to develop a DNA-methylation predictor of Pace-of-Aging, called DunedinPoAm for Dunedin(P)ace(o)f(A)ging(m)ethylation. Validation analysis in cohort studies and the CALERIE trial provide proof-of-principle for DunedinPoAm as a single-time-point measure of a person’s pace of biological aging. more...
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- 2020
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12. Specific microRNA signatures in exosomes of triple-negative and HER2-positive breast cancer patients undergoing neoadjuvant therapy within the GeparSixto trial
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Ines Stevic, Volkmar Müller, Karsten Weber, Peter A. Fasching, Thomas Karn, Frederic Marmé, Christian Schem, Elmar Stickeler, Carsten Denkert, Marion van Mackelenbergh, Christoph Salat, Andreas Schneeweiss, Klaus Pantel, Sibylle Loibl, Michael Untch, and Heidi Schwarzenbach more...
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MicroRNAs ,Exosomes ,Breast cancer ,Triple negative ,HER2-positive ,Pathological complete response ,Medicine - Abstract
Abstract Background The focus of this study is to identify particular microRNA (miRNA) signatures in exosomes derived from plasma of 435 human epidermal growth factor receptor 2 (HER2)-positive and triple-negative (TN) subtypes of breast cancer (BC). Methods First, miRNA expression profiles were determined in exosomes derived from the plasma of 15 TNBC patients before neoadjuvant therapy using a quantitative TaqMan real-time PCR-based microRNA array card containing 384 different miRNAs. Forty-five miRNAs associated with different clinical parameters were then selected and mounted on microRNA array cards that served for the quantification of exosomal miRNAs in 435 BC patients before therapy and 20 healthy women. Confocal microscopy, Western blot, and ELISA were used for exosome characterization. Results Quantification of 45 exosomal miRNAs showed that compared with healthy women, 10 miRNAs in the entire cohort of BC patients, 13 in the subgroup of 211 HER2-positive BC, and 17 in the subgroup of 224 TNBC were significantly deregulated. Plasma levels of 18 exosomal miRNAs differed between HER2-positive and TNBC subtypes, and 9 miRNAs of them also differed from healthy women. Exosomal miRNAs were significantly associated with the clinicopathological and risk factors. In uni- and multivariate models, miR-155 (p = 0.002, p = 0.003, respectively) and miR-301 (p = 0.002, p = 0.001, respectively) best predicted pathological complete response (pCR). Conclusion Our findings show a network of deregulated exosomal miRNAs with specific expression patterns in exosomes of HER2-positive and TNBC patients that are also associated with clinicopathological parameters and pCR within each BC subtype. more...
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- 2018
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13. Sex-associated differences in mitochondrial function in human peripheral blood mononuclear cells (PBMCs) and brain
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C. Silaidos, U. Pilatus, R. Grewal, S. Matura, B. Lienerth, J. Pantel, and G. P. Eckert
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Sex differences ,Blood cells ,MR spectroscopy ,Mitochondria ,Mitochondrial respiration ,N-Acetylaspartate ,Medicine ,Physiology ,QP1-981 - Abstract
Abstract Background Alzheimer’s disease (AD) is the most common form of dementia, and it affects more women than men. Mitochondrial dysfunction (MD) plays a key role in AD, and it is detectable at an early stage of the degenerative process in peripheral tissues, such as peripheral mononuclear blood cells (PBMCs). However, whether these changes are also reflected in cerebral energy metabolism and whether sex-specific differences in mitochondrial function occur are not clear. Therefore, we estimated the correlation between mitochondrial function in PBMCs and brain energy metabolites and examined sex-specific differences in healthy participants to elucidate these issues. Methods The current pilot study included 9 male and 15 female healthy adults (mean age 30.8 ± 7.1 years). Respiration and activity of mitochondrial respiratory complexes were measured using a Clarke-electrode (Oxygraph-2k system), and adenosine triphosphate (ATP) levels were determined using a bioluminescence-based assay in isolated PBMCs. Citrate synthase activity as a mitochondrial marker was measured using a photometric assay. Concentrations of brain energy metabolites were quantified in the same individuals using 1H-magnetic resonance spectroscopy (MRS). Results We detected sex-associated differences in mitochondrial function. Mitochondrial complexes I, I+II, and IV and uncoupled respiration and electron transport system (ETS) capacity in PBMCs isolated from blood samples of females were significantly (p 50%) of gray matter (GM) (p more...
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- 2018
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14. Combined Quantification of 18F-FDG and 68Ga-DOTATATE PET/CT for Prognosis in High-Grade Gastroenteropancreatic Neuroendocrine Neoplasms
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Stephen E. Moore, Jennifer R. Eads, Carina Mari Aparici, Hwan Lee, Ryusuke Nakamoto, Daniel A. Pryma, and Austin R. Pantel
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Oncology ,medicine.medical_specialty ,PET-CT ,business.industry ,Proportional hazards model ,External validation ,Neuroendocrine tumors ,medicine.disease ,Well differentiated ,Internal medicine ,Cohort ,medicine ,Ki67 index ,Radiology, Nuclear Medicine and imaging ,68Ga-DOTATATE ,business - Abstract
Rationale and Objectives High-grade gastroenteropancreatic neuroendocrine neoplasms (G3 GEP-NENs) are pathologically classified into well differentiated neuroendocrine tumors (G3 NETs) and poorly differentiated neuroendocrine carcinomas (G3 NECs). Using a novel parameter, we examined the prognostic value of 18F-FDG and 68Ga-DOTATATE PET/CT quantification in comparison to pathologic assessment in G3 GEP-NENs. Materials and Methods A total of 31 patients with G3 GEP-NENs were reviewed. For each patient, the SUVmax on 18F-FDG and 68Ga-DOTATATE PET/CT were used to calculate the FDG-DOTATATE-Z (FDZ) score: a continuous parameter that increases with 68Ga-DOTATATE uptake and decreases with 18F-FDG uptake. The variation in the FDZ score with respect to pathologic variables was examined. Kaplan-Meier and Cox regression analyses were performed to evaluate the effect of FDZ score on overall survival. An external cohort of 21 patients was used for validation. Results The FDZ score was significantly higher in G3 NETs compared to G3 NECs (p 0.05 group showed significantly longer survival compared to those in the FDZ≤0.05 group, with median of 34.9 vs. 12.0 months (p 0.05 (p=0.005), well differentiated disease (p=0.044), and lower Ki67 index (p=0.042) were predictors of survival. On multivariate regression, only FDZ>0.05 could independently predict longer survival with HR=0.16 (p=0.018), which was reproduced in the external validation cohort. Conclusion Combined quantification of 18F-FDG and 68Ga-DOTATATE PET/CT into a novel parameter, the FDZ score, reflects the pathologic characteristics of G3 GEP-NENs and is a prognostic indicator of overall survival independent of differentiation. more...
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- 2022
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15. Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
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Niamh Mullins, JooEun Kang, Adrian I. Campos, Jonathan R.I. Coleman, Alexis C. Edwards, Hanga Galfalvy, Daniel F. Levey, Adriana Lori, Andrey Shabalin, Anna Starnawska, Mei-Hsin Su, Hunna J. Watson, Mark Adams, Swapnil Awasthi, Michael Gandal, Jonathan D. Hafferty, Akitoyo Hishimoto, Minsoo Kim, Satoshi Okazaki, Ikuo Otsuka, Stephan Ripke, Erin B. Ware, Andrew W. Bergen, Wade H. Berrettini, Martin Bohus, Harry Brandt, Xiao Chang, Wei J. Chen, Hsi-Chung Chen, Steven Crawford, Scott Crow, Emily DiBlasi, Philibert Duriez, Fernando Fernández-Aranda, Manfred M. Fichter, Steven Gallinger, Stephen J. Glatt, Philip Gorwood, Yiran Guo, Hakon Hakonarson, Katherine A. Halmi, Hai-Gwo Hwu, Sonia Jain, Stéphane Jamain, Susana Jiménez-Murcia, Craig Johnson, Allan S. Kaplan, Walter H. Kaye, Pamela K. Keel, James L. Kennedy, Kelly L. Klump, Dong Li, Shih-Cheng Liao, Klaus Lieb, Lisa Lilenfeld, Chih-Min Liu, Pierre J. Magistretti, Christian R. Marshall, James E. Mitchell, Eric T. Monson, Richard M. Myers, Dalila Pinto, Abigail Powers, Nicolas Ramoz, Stefan Roepke, Vsevolod Rozanov, Stephen W. Scherer, Christian Schmahl, Marcus Sokolowski, Michael Strober, Laura M. Thornton, Janet Treasure, Ming T. Tsuang, Stephanie H. Witt, D. Blake Woodside, Zeynep Yilmaz, Lea Zillich, Rolf Adolfsson, Ingrid Agartz, Tracy M. Air, Martin Alda, Lars Alfredsson, Ole A. Andreassen, Adebayo Anjorin, Vivek Appadurai, María Soler Artigas, Sandra Van der Auwera, M. Helena Azevedo, Nicholas Bass, Claiton H.D. Bau, Bernhard T. Baune, Frank Bellivier, Klaus Berger, Joanna M. Biernacka, Tim B. Bigdeli, Elisabeth B. Binder, Michael Boehnke, Marco P. Boks, Rosa Bosch, David L. Braff, Richard Bryant, Monika Budde, Enda M. Byrne, Wiepke Cahn, Miguel Casas, Enrique Castelao, Jorge A. Cervilla, Boris Chaumette, Sven Cichon, Aiden Corvin, Nicholas Craddock, David Craig, Franziska Degenhardt, Srdjan Djurovic, Howard J. Edenberg, Ayman H. Fanous, Jerome C. Foo, Andreas J. Forstner, Mark Frye, Janice M. Fullerton, Justine M. Gatt, Pablo V. Gejman, Ina Giegling, Hans J. Grabe, Melissa J. Green, Eugenio H. Grevet, Maria Grigoroiu-Serbanescu, Blanca Gutierrez, Jose Guzman-Parra, Steven P. Hamilton, Marian L. Hamshere, Annette Hartmann, Joanna Hauser, Stefanie Heilmann-Heimbach, Per Hoffmann, Marcus Ising, Ian Jones, Lisa A. Jones, Lina Jonsson, René S. Kahn, John R. Kelsoe, Kenneth S. Kendler, Stefan Kloiber, Karestan C. Koenen, Manolis Kogevinas, Bettina Konte, Marie-Odile Krebs, Mikael Landén, Jacob Lawrence, Marion Leboyer, Phil H. Lee, Douglas F. Levinson, Calwing Liao, Jolanta Lissowska, Susanne Lucae, Fermin Mayoral, Susan L. McElroy, Patrick McGrath, Peter McGuffin, Andrew McQuillin, Sarah E. Medland, Divya Mehta, Ingrid Melle, Yuri Milaneschi, Philip B. Mitchell, Esther Molina, Gunnar Morken, Preben Bo Mortensen, Bertram Müller-Myhsok, Caroline Nievergelt, Vishwajit Nimgaonkar, Markus M. Nöthen, Michael C. O’Donovan, Roel A. Ophoff, Michael J. Owen, Carlos Pato, Michele T. Pato, Brenda W.J.H. Penninx, Jonathan Pimm, Giorgio Pistis, James B. Potash, Robert A. Power, Martin Preisig, Digby Quested, Josep Antoni Ramos-Quiroga, Andreas Reif, Marta Ribasés, Vanesa Richarte, Marcella Rietschel, Margarita Rivera, Andrea Roberts, Gloria Roberts, Guy A. Rouleau, Diego L. Rovaris, Dan Rujescu, Cristina Sánchez-Mora, Alan R. Sanders, Peter R. Schofield, Thomas G. Schulze, Laura J. Scott, Alessandro Serretti, Jianxin Shi, Stanley I. Shyn, Lea Sirignano, Pamela Sklar, Olav B. Smeland, Jordan W. Smoller, Edmund J.S. Sonuga-Barke, Gianfranco Spalletta, John S. Strauss, Beata Świątkowska, Maciej Trzaskowski, Gustavo Turecki, Laura Vilar-Ribó, John B. Vincent, Henry Völzke, James T.R. Walters, Cynthia Shannon Weickert, Thomas W. Weickert, Myrna M. Weissman, Leanne M. Williams, Naomi R. Wray, Clement C. Zai, Allison E. Ashley-Koch, Jean C. Beckham, Elizabeth R. Hauser, Michael A. Hauser, Nathan A. Kimbrel, Jennifer H. Lindquist, Benjamin McMahon, David W. Oslin, Xuejun Qin, Esben Agerbo, Anders D. Børglum, Gerome Breen, Annette Erlangsen, Tõnu Esko, Joel Gelernter, David M. Hougaard, Ronald C. Kessler, Henry R. Kranzler, Qingqin S. Li, Nicholas G. Martin, Andrew M. McIntosh, Ole Mors, Merete Nordentoft, Catherine M. Olsen, David Porteous, Robert J. Ursano, Danuta Wasserman, Thomas Werge, David C. Whiteman, Cynthia M. Bulik, Hilary Coon, Ditte Demontis, Anna R. Docherty, Po-Hsiu Kuo, Cathryn M. Lewis, J. John Mann, Miguel E. Rentería, Daniel J. Smith, Eli A. Stahl, Murray B. Stein, Fabian Streit, Virginia Willour, Douglas M. Ruderfer, Manuel Mattheisen, Abdel Abdellaoui, Mark J. Adams, Till F.M. Andlauer, Silviu-Alin Bacanu, Marie Bækvad-Hansen, Aartjan T.F. Beekman, Julien Bryois, Henriette N. Buttenschøn, Jonas Bybjerg-Grauholm, Na Cai, Jane Hvarregaard Christensen, Toni-Kim Clarke, Lucía Colodro-Conde, Baptiste Couvy-Duchesne, Nick Craddock, Gregory E. Crawford, Gail Davies, Eske M. Derks, Nese Direk, Conor V. Dolan, Erin C. Dunn, Thalia C. Eley, Valentina Escott-Price, Farnush Farhadi Hassan Kiadeh, Hilary K. Finucane, Josef Frank, Héléna A. Gaspar, Michael Gill, Fernando S. Goes, Scott D. Gordon, Shantel Marie Weinsheimer, Jürgen Wellmann, Gonneke Willemsen, Yang Wu, Hualin S. Xi, Jian Yang, Futao Zhang, Volker Arolt, Dorret I. Boomsma, Udo Dannlowski, E.J.C. de Geus, J. Raymond Depaulo, Enrico Domenici, Katharina Domschke, Jakob Grove, Lynsey S. Hall, Christine Søholm Hansen, Thomas F. Hansen, Stefan Herms, Ian B. Hickie, Georg Homuth, Carsten Horn, Jouke-Jan Hottenga, David M. Howard, Rick Jansen, Eric Jorgenson, James A. Knowles, Isaac S. Kohane, Julia Kraft, Warren W. Kretzschmar, Zoltán Kutalik, Yihan Li, Penelope A. Lind, Donald J. MacIntyre, Dean F. MacKinnon, Robert M. Maier, Wolfgang Maier, Jonathan Marchini, Hamdi Mbarek, Christel M. Middeldorp, Evelin Mihailov, Lili Milani, Francis M. Mondimore, Grant W. Montgomery, Sara Mostafavi, Matthias Nauck, Bernard Ng, Michel G. Nivard, Dale R. 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J., Wasserman, D., Coon, H., Demontis, D., Docherty, A. R., Kuo, P. -H., Mann, J. J., Renteria, M. E., Stein, M. B., Willour, V., Psychiatry, Biological Psychology, APH - Methodology, APH - Mental Health, APH - Health Behaviors & Chronic Diseases, AMS - Sports, AMS - Ageing & Vitality, APH - Personalized Medicine, Amsterdam Neuroscience - Complex Trait Genetics, Complex Trait Genetics, Institute for Molecular Medicine Finland, Centre of Excellence in Complex Disease Genetics, Aarno Palotie / Principal Investigator, Genomics of Neurological and Neuropsychiatric Disorders, HUS Psychiatry, Department of Public Health, Clinicum, Nuorisopsykiatria, Faculty Common Matters (Faculty of Social Sciences), Samuli Olli Ripatti / Principal Investigator, Complex Disease Genetics, Biostatistics Helsinki, Anna Keski-Rahkonen / Principal Investigator, Elisabeth Ingrid Maria Widen / Principal Investigator, Genomic Discoveries and Clinical Translation, Internal medicine, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Digital Health, Mullins N., Kang J., Campos A.I., Coleman J.R.I., Edwards 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Artigas M., Van der Auwera S., Azevedo M.H., Bass N., Bau C.H.D., Baune B.T., Bellivier F., Berger K., Biernacka J.M., Bigdeli T.B., Binder E.B., Boehnke M., Boks M.P., Bosch R., Braff D.L., Bryant R., Budde M., Byrne E.M., Cahn W., Casas M., Castelao E., Cervilla J.A., Chaumette B., Cichon S., Corvin A., Craddock N., Craig D., Degenhardt F., Djurovic S., Edenberg H.J., Fanous A.H., Foo J.C., Forstner A.J., Frye M., Fullerton J.M., Gatt J.M., Gejman P.V., Giegling I., Grabe H.J., Green M.J., Grevet E.H., Grigoroiu-Serbanescu M., Gutierrez B., Guzman-Parra J., Hamilton S.P., Hamshere M.L., Hartmann A., Hauser J., Heilmann-Heimbach S., Hoffmann P., Ising M., Jones I., Jones L.A., Jonsson L., Kahn R.S., Kelsoe J.R., Kendler K.S., Kloiber S., Koenen K.C., Kogevinas M., Konte B., Krebs M.-O., Landen M., Lawrence J., Leboyer M., Lee P.H., Levinson D.F., Liao C., Lissowska J., Lucae S., Mayoral F., McElroy S.L., McGrath P., McGuffin P., McQuillin A., Medland S.E., Mehta D., Melle I., Milaneschi Y., Mitchell P.B., Molina E., Morken G., Mortensen P.B., Muller-Myhsok B., Nievergelt C., Nimgaonkar V., Nothen M.M., O'Donovan M.C., Ophoff R.A., Owen M.J., Pato C., Pato M.T., Penninx B.W.J.H., Pimm J., Pistis G., Potash J.B., Power R.A., Preisig M., Quested D., Ramos-Quiroga J.A., Reif A., Ribases M., Richarte V., Rietschel M., Rivera M., Roberts A., Roberts G., Rouleau G.A., Rovaris D.L., Rujescu D., Sanchez-Mora C., Sanders A.R., Schofield P.R., Schulze T.G., Scott L.J., Serretti A., Shi J., Shyn S.I., Sirignano L., Sklar P., Smeland O.B., Smoller J.W., Sonuga-Barke E.J.S., Spalletta G., Strauss J.S., Swiatkowska B., Trzaskowski M., Turecki G., Vilar-Ribo L., Vincent J.B., Volzke H., Walters J.T.R., Shannon Weickert C., Weickert T.W., Weissman M.M., Williams L.M., Wray N.R., Zai C.C., Ashley-Koch A.E., Beckham J.C., Hauser E.R., Hauser M.A., Kimbrel N.A., Lindquist J.H., McMahon B., Oslin D.W., Qin X., Mattheisen M., Abdellaoui A., Adams M.J., Agerbo E., Andlauer T.F.M., Bacanu S.-A., Baekvad-Hansen M., Beekman A.T.F., Bryois J., Buttenschon H.N., Bybjerg-Grauholm J., Cai N., Christensen J.H., Clarke T.-K., Colodro-Conde L., Couvy-Duchesne B., Crawford G.E., Davies G., Derks E.M., Direk N., Dolan C.V., Dunn E.C., Eley T.C., Escott-Price V., Hassan Kiadeh F.F., Finucane H.K., Frank J., Gaspar H.A., Gill M., Goes F.S., Gordon S.D., Weinsheimer S.M., Wellmann J., Willemsen G., Wu Y., Xi H.S., Yang J., Zhang F., Arolt V., Boomsma D.I., Dannlowski U., de Geus E.J.C., Depaulo J.R., Domenici E., Domschke K., Esko T., Grove J., Hall L.S., Hansen C.S., Hansen T.F., Herms S., Hickie I.B., Homuth G., Horn C., Hottenga J.-J., Hougaard D.M., Howard D.M., Jansen R., Jorgenson E., Knowles J.A., Kohane I.S., Kraft J., Kretzschmar W.W., Kutalik Z., Li Y., Lind P.A., MacIntyre D.J., MacKinnon D.F., Maier R.M., Maier W., Marchini J., Mbarek H., Middeldorp C.M., Mihailov E., Milani L., Mondimore F.M., Montgomery G.W., Mostafavi S., Nauck M., Ng B., Nivard M.G., Nyholt D.R., O'Reilly P.F., Oskarsson H., Hayward C., Heath A.C., Lewis G., Li Q.S., Madden P.A.F., Magnusson P.K., Martin N.G., McIntosh A.M., Metspalu A., Mors O., Nordentoft M., Paciga S.A., Pedersen N.L., Painter J.N., Pedersen C.B., Pedersen M.G., Peterson R.E., Peyrot W.J., Posthuma D., Quiroz J.A., Qvist P., Rice J.P., Riley B.P., Mirza S.S., Schoevers R., Schulte E.C., Shen L., Sigurdsson E., Sinnamon G.C.B., Smit J.H., Smith D.J., Stefansson H., Steinberg S., Streit F., Strohmaier J., Tansey K.E., Teismann H., Teumer A., Thompson W., Thomson P.A., Thorgeirsson T.E., Traylor M., Treutlein J., Trubetskoy V., Uitterlinden A.G., Umbricht D., der Auwera S.V., van Hemert A.M., Viktorin A., Visscher P.M., Wang Y., Webb B.T., Perlis R.H., Porteous D.J., Schaefer C., Stefansson K., Tiemeier H., Uher R., Werge T., Lewis C.M., Breen G., Borglum A.D., Sullivan P.F., O'Connell K.S., Coombes B., Qiao Z., Als T.D., Borte S., Charney A.W., Drange O.K., Gandal M.J., Hagenaars S.P., Ikeda M., Kamitaki N., Krebs K., Panagiotaropoulou G., Schilder B.M., Sloofman L.G., Winsvold B.S., Won H.-H., Abramova L., Adorjan K., Al Eissa M., Albani D., Alliey-Rodriguez N., Antilla V., Antoniou A., Baek J.H., Bauer M., Beins E.C., Bergen S.E., Birner A., Boen E., Brum M., Brumpton B.M., Brunkhorst-Kanaan N., Byerley W., Cairns M., Cervantes P., Cruceanu C., Cuellar-Barboza A., Cunningham J., Curtis D., Czerski P.M., Dale A.M., Dalkner N., David F.S., Dobbyn A.L., Douzenis A., Elvsashagen T., Ferrier I.N., Fiorentino A., Foroud T.M., Forty L., Frei O., Freimer N.B., Frisen L., Gade K., Garnham J., Gelernter J., Gizer I.R., Gordon-Smith K., Greenwood T.A., Ha K., Haraldsson M., Hautzinger M., Heilbronner U., Hellgren D., Holmans P.A., Huckins L., Johnson J.S., Kalman J.L., Kamatani Y., Kittel-Schneider S., Koromina M., Kranz T.M., Kranzler H.R., Kubo M., Kupka R., Kushner S.A., Lavebratt C., Leber M., Lee H.-J., Levy S.E., Lewis C., Lundberg M., Magnusson S.H., Maihofer A., Malaspina D., Maratou E., Martinsson L., McGregor N.W., McKay J.D., Medeiros H., Millischer V., Moran J.L., Morris D.W., Muhleisen T.W., O'Brien N., O'Donovan C., Olde Loohuis L.M., Oruc L., Papiol S., Pardinas A.F., Perry A., Pfennig A., Porichi E., Raj T., Rapaport M.H., Regeer E.J., Rivas F., Roth J., Roussos P., Ruderfer D.M., Senner F., Sharp S., Shilling P.D., Slaney C., Sobell J.L., Artigas M.S., Spijker A.T., Stein D.J., Terao C., Toma C., Tooney P., Tsermpini E.-E., Vawter M.P., Vedder H., Xi S., Xu W., Kay Yang J.M., Young A.H., Young H., Zandi P.P., Zhou H., HUNT All-In Psychiatry, Babadjanova G., Backlund L., Bengesser S., Blackwood D.H.R., Carr V.J., Catts S., Dikeos D., Etain B., Ferentinos P., Gawlik M., Gershon E.S., Henskens F., Hillert J., Hong K.S., Hultman C.M., Hveem K., Iwata N., Jablensky A.V., Kirov G., Lochner C., Loughland C., Mathews C.A., McMahon F.J., Michie P., Mowry B., Neale B.M., Nievergelt C.M., Oedegaard K.J., Olsson T., Pantelis C., Patrinos G.P., Reininghaus E.Z., Saito T., Schall U., Schalling M., Scott R.J., Weickert C.S., Stordal E., Vaaler A.E., Vieta E., Waldman I.D., Zwart J.-A., Nurnberger J.I., Stahl E.A., Di Florio A., Adan R.A.H., Ando T., Aschauer H., Baker J.H., Bencko V., Birgegard A., Boden J.M., Boehm I., Boni C., Perica V.B., Buehren K., Bulik C.M., Burghardt R., Carlberg L., Cassina M., Clementi M., Cone R.D., Courtet P., Crowley J.J., Danner U.N., Davis O.S.P., de Zwaan M., Dedoussis G., Degortes D., DeSocio J.E., Dick D.M., Dina C., Dmitrzak-Weglarz M., Martinez E.D., Duncan L.E., Egberts K., Mattingsdal M., McDevitt S., Meulenbelt I., Micali N., Mitchell J., Mitchell K., Monteleone P., Monteleone A.M., Munn-Chernoff M.A., Nacmias B., Navratilova M., Ntalla I., Olsen C.M., O'Toole J.K., Padyukov L., Palotie A., Pantel J., Papezova H., Parker R., Pearson J.F., Ehrlich S., Escaramis G., Espeseth T., Estivill X., Farmer A., Favaro A., Fischer K., Floyd J.A.B., Focker M., Foretova L., Forzan M., Franklin C.S., Gambaro G., Giuranna J., Giusti-Rodriquez P., Gonidakis F., Gordon S., Mayora M.G., Guillaume S., Hanscombe K.B., Hatzikotoulas K., Hebebrand J., Helder S.G., Henders A.K., Herpertz-Dahlmann B., Herzog W., Hinney A., Horwood L.J., Hubel C., Petersen L.V., Purves K.L., Raevuori A., Reichborn-Kjennerud T., Ricca V., Ripatti S., Ritschel F., Roberts M., Rybakowski F., Santonastaso P., Scherag A., Schmidt U., Schork N.J., Schosser A., Seitz J., Slachtova L., Slagboom P.E., Slof-Op 't Landt M.C.T., Slopien A., Soranzo N., Sorbi S., Southam L., Steen V.W., Huckins L.M., Hudson J.I., Imgart H., Inoko H., Janout V., Jordan J., Julia A., Kalsi G., Kaminska D., Kaprio J., Karhunen L., Karwautz A., Kas M.J.H., Kennedy M.A., Keski-Rahkonen A., Kiezebrink K., Kim Y.-R., Kirk K.M., Klareskog L., Knudsen G.P.S., Larsen J.T., Le Hellard S., Leppa V.M., Lichtenstein P., Lin B.D., Lundervold A., Luykx J., Maj M., Mannik K., Marsal S., Stuber G.D., Szatkiewicz J.P., Tachmazidou I., Tenconi E., Tortorella A., Tozzi F., Tsitsika A., Tyszkiewicz-Nwafor M., Tziouvas K., van Elburg A.A., van Furth E.F., Wade T.D., Wagner G., Walton E., Whiteman D.C., Wichmann H.E., Widen E., Yao S., Zeggini E., Zerwas S., Zipfel S., Jungkunz M., Dietl L., Schwarze C.E., Dahmen N., Schott B.H., Mobascher A., Crivelli S., Dennis M.F., Harvey P.D., Carter B.W., Huffman J.E., Jacobson D., Madduri R., Olsen M.K., Pestian J., Gaziano J.M., Muralidhar S., Ramoni R., Beckham J., Chang K.-M., O'Donnell C.J., Tsao P.S., Breeling J., Huang G., Romero J.P.C., Moser J., Whitbourne S.B., Brewer J.V., Aslan M., Connor T., Argyres D.P., Stephens B., Brophy M.T., Humphries D.E., Selva L.E., Do N., Shayan S., Cho K., Pyarajan S., Hauser E., Sun Y., Zhao H., Wilson P., McArdle R., Dellitalia L., Mattocks K., Harley J., Zablocki C.J., Whittle J., Jacono F., Gutierrez S., Gibson G., Hammer K., Kaminsky L., Villareal G., Kinlay S., Xu J., Hamner M., Mathew R., Bhushan S., Iruvanti P., Godschalk M., Ballas Z., Ivins D., Mastorides S., Moorman J., Gappy S., Klein J., Ratcliffe N., Florez H., Okusaga O., Murdoch M., Sriram P., Yeh S.S., Tandon N., Jhala D., Aguayo S., Cohen D., Sharma S., Liangpunsakul S., Oursler K.A., Whooley M., Ahuja S., Constans J., Meyer P., Greco J., Rauchman M., Servatius R., Gaddy M., Wallbom A., Morgan T., Stapley T., Sherman S., Ross G., Tsao P., Strollo P., Boyko E., Meyer L., Gupta S., Huq M., Fayad J., Hung A., Lichy J., Hurley R., Robey B., Striker R., Erlangsen A., Kessler R.C., Porteous D., Ursano R.J., Wasserman D., Coon H., Demontis D., Docherty A.R., Kuo P.-H., Mann J.J., Renteria M.E., Stein M.B., and Willour V. more...
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LD SCORE REGRESSION ,Genome-wide association study ,Suicide, Attempted ,3124 Neurology and psychiatry ,0302 clinical medicine ,Risk Factors ,Insomnia ,Suicide attempt ,GWAS ,Suïcidi ,Depression (differential diagnoses) ,Cause of death ,Psychiatry ,0303 health sciences ,Factors de risc en les malalties ,Mental Disorders ,Genetic Correlation ,Genome-wide Association Study ,Pleiotropy ,Polygenicity ,Suicide ,Suicide Attempt ,DEPRESSION ,3. Good health ,Genetic correlation ,Genome-Wide Association Study ,Humans ,Polymorphism, Single Nucleotide ,Depressive Disorder, Major ,Mental illness ,Cohort ,SEX ,medicine.symptom ,Human ,medicine.medical_specialty ,Risk factors in diseases ,BF ,Locus (genetics) ,BEHAVIORS ,Psykiatri ,EVENTS ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,medicine ,ddc:610 ,GENOME-WIDE ASSOCIATION ,IDEATION ,Socioeconomic status ,METAANALYSIS ,Biological Psychiatry ,030304 developmental biology ,business.industry ,Risk Factor ,Genetic architecture ,THOUGHTS ,RC0321 ,business ,Malalties mentals ,030217 neurology & neurosurgery - Abstract
Statistical analyses were carried out on the NL Genetic Cluster Computer (http://www.geneticcluster.org) hosted by SURFsara and the Mount Sinai high performance computing cluster (http://hpc.mssm.edu), which is supported by the Office of Research Infrastructure of the National Institutes of Health (Grant Nos. S10OD018522 and S10OD026880). This work was conducted in part using the resources of the Advanced Computing Center for Research and Education at Vanderbilt University, Nashville, TN. This work was funded by the National Institutes of Health (Grant Nos. R01MH116269 and R01MH121455 [to DMR]), NIGMS of the National Institutes of Health (Grant No. T32GM007347 [to JK]), and the Brain & Behavior Research Foundation (NARSAD Young Investigator Award No. 29551 [to NM])., BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders., Office of Research Infrastructure of the National Institutes of Health S10OD018522 S10OD026880, United States Department of Health & Human Services, National Institutes of Health (NIH) - USA R01MH116269 R01MH121455, NIH National Institute of General Medical Sciences (NIGMS) T32GM007347 NARSAD 29551 more...
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- 2022
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16. Clinical management and biology of tumor dormancy in breast cancer
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Isabel Heidrich, Klaus Pantel, and Stefan Werner
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Subsequent Relapse ,Clinical Decision-Making ,Breast Neoplasms ,Disease ,Biology ,03 medical and health sciences ,0302 clinical medicine ,Circulating tumor cell ,Breast cancer ,Internal medicine ,Tumor Microenvironment ,medicine ,Humans ,Liquid biopsy ,Disease Management ,Cancer ,medicine.disease ,Primary tumor ,Minimal residual disease ,3. Good health ,030104 developmental biology ,030220 oncology & carcinogenesis ,Female ,Disease Susceptibility - Abstract
Clinical tumor dormancy is specified as an extended latency period between removal of the primary tumor and subsequent relapse in a cancer patient who has been clinically disease-free. In particular, patients with estrogen receptor-positive breast cancer can undergo extended periods of more than five years before they relapse with overt metastatic disease. Recent studies have shown that minimal residual disease in breast cancer patients can be monitored by different liquid biopsy approaches like analysis of circulating tumor cells or cell-free tumor DNA. Even though the biological principles underlying tumor dormancy in breast cancer patients remain largely unknown, clinical observations and experimental studies have identified emerging mechanisms that control the state of tumor dormancy. In this review, we illustrate the latest discoveries on different molecular aspects that contribute to the control of tumor dormancy and distant metastatic relapse, then discuss current treatments affecting minimal residual disease and dormant cancer cells, and finally highlight how novel liquid biopsy based diagnostic methodologies can be integrated into the detection and molecular characterization of minimal residual disease. more...
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- 2022
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17. Current and Future Clinical Applications of ctDNA in Immuno-Oncology
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Klaus Pantel, Isabel Heidrich, Julia Christina Stadler, Benjamin Deitert, Yassine Belloum, Laura Keller, Mark Sementsov, and Christoffer Gebhardt
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Oncology ,Cancer Research ,medicine.medical_specialty ,Colorectal cancer ,business.industry ,Surrogate endpoint ,medicine.medical_treatment ,Melanoma ,Cancer ,Immunotherapy ,medicine.disease ,Circulating Tumor DNA ,Clinical trial ,Cancer immunotherapy ,Internal medicine ,Biomarkers, Tumor ,medicine ,Humans ,Biomarker (medicine) ,business - Abstract
Testing peripheral blood for circulating tumor DNA (ctDNA) offers a minimally invasive opportunity to diagnose, characterize, and monitor the disease in individual cancer patients. ctDNA can reflect the actual tumor burden and specific genomic state of disease and thus might serve as a prognostic and predictive biomarker for immune checkpoint inhibitor (ICI) therapy. Recent studies in various cancer entities (e.g., melanoma, non–small cell lung cancer, colon cancer, and urothelial cancer) have shown that sequential ctDNA analyses allow for the identification of responders to ICI therapy, with a significant lead time to imaging. ctDNA assessment may also help distinguish pseudoprogression under ICI therapy from real progression. Developing dynamic changes in ctDNA concentrations as a potential surrogate endpoint of clinical efficacy in patients undergoing adjuvant immunotherapy is ongoing. Besides overall ctDNA burden, further ctDNA characterization can help uncover tumor-specific determinants (e.g., tumor mutational burden and microsatellite instability) of responses or resistance to immunotherapy. In future studies, standardized ctDNA assessments need to be included in interventional clinical trials across cancer entities to demonstrate the clinical utility of ctDNA as a biomarker for personalized cancer immunotherapy. more...
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- 2021
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18. Molecular mechanisms of cancer metastasis via the lymphatic versus the blood vessels
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Marlys H. Witte, Kamila Naxerova, Laura Keller, Klaus Pantel, and Stanley P. L. Leong
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Cancer Research ,Sentinel Lymph Node Biopsy ,business.industry ,Sentinel lymph node ,Cancer ,General Medicine ,medicine.disease ,Lymphangiogenesis ,Metastasis ,Lymphatic System ,medicine.anatomical_structure ,Breast cancer ,Lymphatic system ,Oncology ,Lymphatic Metastasis ,Cancer cell ,medicine ,Cancer research ,Humans ,Lymph Nodes ,business ,Melanoma ,Lymph node ,Lymphatic Vessels - Abstract
Cancer metastasis is the process by which primary cancer cells invade through the lymphatic or blood vessels to distant sites. The molecular mechanisms by which cancer cells spread either through the lymphatic versus blood vessels or both are not well established. Two major developments have helped us to understand the process more clearly. First, the development of the sentinel lymph node (SLN) concept which is well established in melanoma and breast cancer. The SLN is the first lymph node in the draining nodal basin to receive cancer cells. Patients with a negative SLN biopsy show a significantly lower incidence of distant metastasis, suggesting that the SLN may be the major gateway for cancer metastasis in these cancer types. Second, the discovery and characterization of several biomarkers including VEGF-C, LYVE-1, Podoplanin and Prox-1 have opened new vistas in the understanding of the induction of lymphangiogenesis by cancer cells. Cancer cells must complete multiple steps to invade the lymphatic system, some of which may be enabled by the evolution of new traits during cancer progression. Thus, cancer cells may spread initially through the main gateway of the SLN, from which evolving cancer clones can invade the blood vessels to distant sites. Cancer cells may also enter the blood vessels directly, bypassing the SLN to establish distant metastases. Future studies need to pinpoint the molecules that are used by cancer cells at different stages of metastasis via different routes so that specific therapies can be targeted against these molecules, with the goal of stopping or preventing cancer metastasis. more...
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- 2021
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19. Einwilligung von Menschen mit Demenz in medizinische Maßnahmen
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Johannes Pantel, Julia Haberstroh, and Valentina A. Tesky
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business.industry ,Medicine ,business - Published
- 2021
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20. Person-environment fit of environmental support provided during medical consultations with older patients
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Frank Oswald, Aoife Poth, Valentina A. Tesky, Meret Baumgardt, Julia Haberstroh, and Johannes Pantel
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medicine.medical_specialty ,Health (social science) ,Medical treatment ,Cognition ,Survey research ,medicine.disease ,Environmental support ,Comprehension ,Issues, ethics and legal aspects ,Older patients ,Acquired immunodeficiency syndrome (AIDS) ,Family medicine ,medicine ,Person–environment fit ,Geriatrics and Gerontology ,Psychology ,Gerontology - Abstract
As some cognitive functions decline in old age, the ability to decide about important life events such as medical treatment is endangered. Environmental support to improve the comprehension of health-related information is therefore necessary. With a small-scale explorative approach, the present survey study aimed at investigating person-environment fit (PE-fit) of support provided during medical consultations. This fit was calculated by assessing the match between aids provided by five medical practitioners during medical consultations and aids most appreciated by the geriatric patients (N = 88). The results showed that the largest discrepancies of used and appreciated aids could be found concerning the opportunity to discuss decisions with relatives, the possibility to take notes, the use of objects, pictures and a keyword list. Female patients indicated a lower PE-fit. These findings highlight discrepancies between the use of specific aids and the wishes of patients and call for thoughtful use of aids during consultations with geriatric patients. more...
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- 2021
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21. Circulating Cellular Communication Network Factor 1 Protein as a Sensitive Liquid Biopsy Marker for Early Detection of Breast Cancer
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Hannah Voß, Maggie Banys-Paluchowski, Isabel Heidrich, Marcel Kwiatkowski, Klaus Pantel, Volkmar Müller, Hartmut Schlüter, Antje Andreas, Maria Geffken, Leticia Oliveira-Ferrer, Sven Peine, Kai Bartkowiak, Simon A. Joosse, Marcus Wurlitzer, Tanja Zeller, and Stefan Blankenberg more...
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Oncology ,medicine.medical_specialty ,medicine.medical_treatment ,Clinical Biochemistry ,Breast Neoplasms ,Breast cancer ,Internal medicine ,Biomarkers, Tumor ,medicine ,Humans ,Blood test ,Stage (cooking) ,Liquid biopsy ,Early Detection of Cancer ,Neoadjuvant therapy ,medicine.diagnostic_test ,Receiver operating characteristic ,business.industry ,Biochemistry (medical) ,Liquid Biopsy ,Area under the curve ,Proteins ,medicine.disease ,Case-Control Studies ,Biomarker (medicine) ,Female ,business ,Biomarkers - Abstract
Background Despite recent progress in liquid biopsy technologies, early blood-based detection of breast cancer is still a challenge. Methods We analyzed secretion of the protein cellular communication network factor 1 (CCN1, formerly cysteine-rich angiogenic inducer 61) in breast cancer cell lines by an enzyme-linked immunosorbent assay (ELISA). Soluble CCN1 in the plasma (2.5 µL) of 544 patients with breast cancer and 427 healthy controls was analyzed by ELISA. The breast cancer samples were acquired at the time of primary diagnosis prior to neoadjuvant therapy or surgery. A classifier was established on a training cohort of patients with breast cancer and age-adapted healthy controls and further validated on an independent cohort comprising breast cancer patients and healthy controls. Samples from patients with benign breast diseases were investigated as additional controls. Samples from patients with acute heart diseases (n = 127) were investigated as noncancer controls. The diagnostic accuracy was determined by receiver operating characteristic using the parameters area under the curve, sensitivity, and specificity. Results CCN1 was frequently secreted by breast cancer cell lines into the extracellular space. Subsequent analysis of clinical blood samples from patients with breast cancer and age-adjusted healthy controls revealed an overall specificity of 99.0% and sensitivity of 80.0% for cancer detection. Remarkably, 81.5% of small T1 cancers were already CCN1-positive, while CCN1 concentrations in patients with benign breast lesions were below the threshold for breast cancer detection. Conclusions Circulating CCN1 is a potentially novel blood biomarker for the detection of breast cancer at the earliest invasive stage. more...
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- 2021
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22. Doing time in care homes: insights into the experiences of care home residents in Germany during the early phase of the COVID-19 pandemic
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Frank Oswald, Johannes Pantel, Arthur Schall, and Miranda Leontowitsch
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Gerontology ,Hierarchy ,Health (social science) ,Social Psychology ,media_common.quotation_subject ,Public Health, Environmental and Occupational Health ,Globe ,Mental health ,medicine.anatomical_structure ,Arts and Humanities (miscellaneous) ,Agency (sociology) ,Structured interview ,Pandemic ,medicine ,Sociology ,Psychological resilience ,Geriatrics and Gerontology ,Social isolation ,medicine.symptom ,media_common - Abstract
Residents of care homes across the globe are affected by the spread of SARS-CoV-2 as they have been identified as a high-risk group and because they experienced strict social isolation regulations during the first wave of the pandemic. Social isolation of older people with poor physical and mental health is strongly associated with mental health problems and decreased life expectancy. Other research has shown that older people managed to adapt to the changes brought about by the pandemic and have linked this to the concept of resilience. The aim of this research project was to investigate how this applied to residents in care home settings during the first phases of the contact ban in Germany from sociology, developmental psychology and environmental gerontology perspectives, and to gain in-depth understanding of residents' experiences. This paper draws on structured interview data collected from residents in two care homes during early June 2020 in Frankfurt am Main, Germany. The findings show that their experiences were shaped by three factors: care home settings and the approach of staff to handling the contact ban;biographical sense of resilience;and a hierarchy of life issues. The findings highlight the importance of locally specific response mechanisms in care homes, agency and belonging of residents despite health-related limitations and the importance of a critical (gendered) lens on understanding their experiences. © The Author(s), 2021. Published by Cambridge University Press. more...
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- 2021
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23. Projeto Córdoba: fronteira em movimento
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Danuza Meneghello, Camilo Buss Araújo, Fabíola Teixeira Ferreira, Rodolfo Pantel, Tomás Fontan, and Lara Lodi da Silva
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Educação ,Fronteira ,Integração ,Cultura ,Medicine ,Science ,Social Sciences - Abstract
Era época de comemorações pelos 500 anos do “descobrimento” e colonização da América, espaço temporal de uma massiva expropriação das riquezas de nosso continente. Para registrar a data, desde 1989 que duas instituições federais de ensino trabalhavam com o objetivo de aproximar dois países, Brasil e Argentina. A ideia, superar desconfianças, divergências, e construir um novo paradigma no sentido de viabilizar uma América Latina possível. Juntos, criar um novo patamar de desenvolvimento social, cultural, educacional. Possibilitar que estudantes e professores do Colégio de Aplicação da Universidade Federal de Santa Catarina e da Escuela Superior de Comercio Manuel Belgrano da Universidad Nacional de Córdoba/Argentina trocassem experiências educacionais e culturais, criando um espaço permanente para pensar a nuestra América. Nosso projeto se contrapõe ao projeto pensado de integração pelo viés comercial, proposto pelo Mercosul. O Acordo de Cooperação entre Brasil e Argentina tem por objetivo a troca de experiências na área científico-pedagógica e o intercâmbio de estudantes, docentes e técnico-administrativos, aprofundando o estreitamento de relações culturais, desvendando elementos integradores e o senso de latino-americanidade. No ano de 1992, através de um processo coletivo e multidisciplinar, conseguimos escrever um documento firmando princípios que consideramos fundamentais para selar esse Acordo de Cooperação. E é desde então que o Projeto Córdoba, como nos denominamos, consiste em um projeto de intercâmbio acadêmico-cultural entre estudantes e professores, que objetiva a troca de experiências, o viver entre os povos de forma integrada, solidária e complementar, respeitando suas individualidades e convivendo com suas (des)semelhanças. É a integração em movimento. more...
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- 2014
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24. A Comprehensive Molecular Analysis of in Vivo Isolated EpCAM-Positive Circulating Tumor Cells in Breast Cancer
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Anna-Lena Bohnen, Klaus Pantel, Galatea Kallergi, Tobias M. Gorges, Vasilis Georgoulias, Andra Kuske, Evi Lianidou, Sabine Riethdorf, Nikiforita Poulakaki, Martha Zavridou, Eleni Politaki, Dimitris Mavroudis, Amanda Psyrri, George Koutsodontis, Areti Strati, E. Kontopodis, Claudia Koch, Simon A. Joosse, and Volkmar Mueller more...
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0301 basic medicine ,Clinical Biochemistry ,Breast Neoplasms ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Circulating tumor cell ,Biomarkers, Tumor ,medicine ,Humans ,Liquid biopsy ,biology ,CD24 ,business.industry ,Biochemistry (medical) ,CD44 ,Liquid Biopsy ,DNA Methylation ,Epithelial Cell Adhesion Molecule ,Neoplastic Cells, Circulating ,medicine.disease ,Metastatic breast cancer ,030104 developmental biology ,030220 oncology & carcinogenesis ,DNA methylation ,Cancer research ,biology.protein ,Female ,business ,Blood drawing - Abstract
Background Circulating tumor cell (CTC) analysis is highly promising for liquid biopsy-based molecular diagnostics. We undertook a comprehensive molecular analysis of in vivo isolated CTCs in breast cancer (BrCa). Methods In vivo isolated CTCs from 42 patients with early and 23 patients with metastatic breast cancer (MBC) were prospectively collected and analyzed for gene expression, DNA mutations, and DNA methylation before and after treatment. 19 healthy donor (HD) samples were analyzed as a control group. In identical blood draws, CTCs were enumerated using CellSearch® and characterized by direct IF staining. Results All 19 HD samples were negative for CK8, CK18, CK19, ERBB2, TWIST1, VEGF, ESR1, PR, and EGFR expression, while CD44, CD24, ALDH1, VIM, and CDH2 expression was normalized to B2M (reference gene). At least one gene was expressed in 23/42 (54.8%) and 8/13 (61.5%) CTCs in early BrCa before and after therapy, and in 20/23 (87.0%) and 5/7 (71.4%) MBC before and after the first cycle of therapy. PIK3CA mutations were detected in 11/42 (26.2%) and 3/13 (23.1%) in vivo isolated CTCs in early BrCa before and after therapy, and in 11/23 (47.8%) and 2/7 (28.6%) MBC, respectively. ESR1 methylation was detected in 5/32 (15.7%) and 1/10 (10.0%) CTCs in early BrCa before and after therapy, and in 3/15(20.0%) MBC before the first line of therapy. The comprehensive molecular analysis of CTC revealed a higher sensitivity in relation to CellSearch or IF staining when based on creatine kinase selection. Conclusions In vivo-CTC isolation in combination with a comprehensive molecular analysis at the gene expression, DNA mutation, and DNA methylation level comprises a highly powerful approach for molecular diagnostic applications using CTCs. more...
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- 2021
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25. 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Following Chimeric Antigen Receptor T-cell Therapy in Large B-cell Lymphoma
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Elise A. Chong, Marco Ruella, Sunita D. Nasta, Jakub Svoboda, Mitchell E. Hughes, Michael D. Farwell, Austin R. Pantel, Mark A. Sellmyer, Adam Bagg, Hatcher J. Ballard, Esin C. Namoglu, and Andrew Ruff more...
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Cancer Research ,education.field_of_study ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Radiography ,Population ,medicine.disease ,Asymptomatic ,Article ,Lymphoma ,Oncology ,immune system diseases ,Positron emission tomography ,Medicine ,Radiology, Nuclear Medicine and imaging ,Chimeric Antigen Receptor T-Cell Therapy ,Radiology ,medicine.symptom ,business ,education ,B-cell lymphoma ,Pseudoprogression - Abstract
PURPOSE: (18) F-Fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) is a well-established imaging modality to assess responses in patients with B-cell neoplasms. However, there is limited information about the utility of FDG PET/CT after chimeric antigen receptor T-cell (CART) therapies for large B-cell lymphomas. In this retrospective analysis, we aimed to evaluate how FDG PET/CT performs in patients receiving commercially available anti-CD19 CART therapies for relapsed/refractory (r/r) large B-cell lymphomas. In addition, we examined the time to repeat scan and the rate of pseudoprogression within this population. Lastly, the rates of radiographic response to CART therapy using FDG PET/CT are reported. PROCEDURES: The pre-treatment and post-treatment scans were analyzed from a selected cohort of 43 patients from a single institution. Patients were stratified by diagnosis of either a first occurrence of diffuse large B-cell lymphoma: de novo diffuse large B-cell lymphoma (DLBCL); or a transformed diffuse large B-cell lymphoma arising from indolent non-Hodgkin lymphoma (t-iNHL). RESULTS: More patients received CART therapy for DLBCL than t-iNHL (65% vs 35%). FDG PET/CT had a 99% sensitivity and 100% specificity for detecting recurrent disease in this group. The median time to initial response assessment was 86 days (IQR 79-91; full range 24-146) after infusion. There were no biopsy-proven cases of pseudoprogression identified. In this selected group of patients, the overall response rate by Lugano 2014 criteria was 56%. All patients with a partial response (N = 6) eventually progressed despite additional therapy. CONCLUSIONS: Due to its excellent test characteristics and ability to detect asymptomatic disease, routine surveillance with PET/CT at 3 months after CART infusion is supported by our data. Earlier PET/CT may be of value in select situations as we did not find any cases of pseudoprogression. more...
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- 2021
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26. Einwilligungsfähigkeit von Menschen mit Demenz
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Julia Haberstroh, Valentina A. Tesky, and Johannes Pantel
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Health (social science) ,030214 geriatrics ,business.industry ,General Medicine ,030227 psychiatry ,Issues, ethics and legal aspects ,03 medical and health sciences ,Psychiatry and Mental health ,0302 clinical medicine ,Neurology ,Medicine ,Neurology (clinical) ,Geriatrics and Gerontology ,business ,Gerontology ,030217 neurology & neurosurgery - Published
- 2021
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27. Does Preoperative Calcium and Calcitriol Decrease Rates of Post-Thyroidectomy Hypocalcemia? A Randomized Clinical Trial
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David M. Brams, Colleen Donahue, Bharat B. Yarlagadda, and Haddon J Pantel
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Male ,Parathyroidectomy ,Calcitriol ,medicine.medical_treatment ,chemistry.chemical_element ,Calcium ,law.invention ,03 medical and health sciences ,Postoperative Complications ,0302 clinical medicine ,Randomized controlled trial ,law ,Clinical endpoint ,Humans ,Medicine ,Prospective Studies ,Prospective cohort study ,Hypocalcemia ,business.industry ,Thyroidectomy ,Middle Aged ,chemistry ,030220 oncology & carcinogenesis ,Anesthesia ,Female ,030211 gastroenterology & hepatology ,Surgery ,business ,Complication ,medicine.drug - Abstract
Background Postoperative hypocalcemia is the most common complication after thyroidectomy. Postoperative supplementation with calcium and calcitriol reduces its occurrence; however, prophylactic preoperative supplementation has not been studied systematically. The primary objective of this study was to determine whether pre- and postoperative calcium and calcitriol supplementation reduces postoperative hypocalcemia after total thyroidectomy compared with postoperative supplementation alone. Study Design We conducted a single-institution prospective randomized trial enrolling 82 patients undergoing total thyroidectomy from July 2017 through May 2019. Those undergoing partial thyroidectomy or concurrent planned parathyroidectomy were excluded. The intervention group started calcitriol 0.25 μg po bid and calcium carbonate 1,500 mg po tid 5 days preoperatively and continued postoperatively. The control group started these medications postoperatively. The primary end point was clinical or biochemical hypocalcemia. Secondary outcomes were postoperative calcium levels, need for intervention, length of stay, and readmission. Results Thirty-eight patients were randomized to the intervention group and 44 to the control group. There were 12 episodes of hypocalcemia; 5 (13.2%) in the intervention and 7 (15.9%) in the control group (p = 0.76). No differences were found in secondary outcomes; including postoperative calcium levels at each measured time point, need for intervention (n = 10 [26.3%], n = 15 [34.1%]; p = 0.48), length of stay (mean [SD] 32.3 [15.6] hours, 30.7 [10.5] hours; p = 0.6), or readmissions (n = 0 [0.0%], n = 3 [6.8%]; p = 0.24). Conclusions Starting supplementation with calcium and calcitriol preoperatively does not reduce postoperative hypocalcemia compared with postoperative supplementation alone after total thyroidectomy. These findings do not support the practice of routine calcium and calcitriol supplementation before total thyroidectomy. more...
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- 2021
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28. Pulmonary Adenocarcinoma Metastasis to the Breast Unexpectedly Discovered on Re-staging 18F-FDG PET/CT in a Woman With a Normal Screening Mammogram
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Debra M. Ikeda, Andrei Iagaru, Andrew N. Kozlov, and Austin R. Pantel
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Pulmonary and Respiratory Medicine ,Cancer Research ,PET-CT ,medicine.medical_specialty ,Screening mammogram ,medicine.diagnostic_test ,business.industry ,Pulmonary adenocarcinoma ,medicine.disease ,Metastasis ,Breast cancer ,Oncology ,medicine ,Mammography ,Fdg pet ct ,Radiology ,Lung cancer ,business - Published
- 2021
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29. Distribution of Toxinogenic Methicillin-Resistant and Methicillin-Susceptible Staphylococcus aureus from Different Ecological Niches in Algeria
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Assia Mairi, Abdelaziz Touati, Alix Pantel, Karima Zenati, Alex Yahiaoui Martinez, Catherine Dunyach-Remy, Albert Sotto, and Jean-Philippe Lavigne
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MRSA-ST80 ,PVL ,TSST-1 ,ecological niches ,Algeria ,one health ,Staphylococcus aureus ,epidemiology ,Medicine - Abstract
The diffusion of Panton−Valentine leukocidin (PVL)−positive methicillin-resistant S. aureus (MRSA) is a health problem in Algeria. The objectives of the study were to investigate the global distribution of methicillin-susceptible S. aureus (MSSA) and MRSA isolates in different ecological niches in this country. In total, 2246 samples were collected from humans, livestock, wild animals, pets, food products and the aquatic environment, from 12 Algerian provinces. A total of 312 S. aureus were detected from 2446 samples (12.7%) in the screened niches. We observed the emergence of toxinogenic S. aureus representing 41% of the isolates. Among them, we noted the diffusion of ST80-IV CA-MRSA PVL + strains isolated in human, animals, and food and genetic diversity of MSSA PVL + isolates. This study suggests an alarming dissemination of MRSA-ST80 PVL + in both human and extra-human sources in Algeria. Moreover, MSSA may become a permanent reservoir of the PVL genes necessary for human infections. more...
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- 2019
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30. Novel approaches to target the microenvironment of bone metastasis
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Klaus Pantel, Aline Bozec, Franz Jakob, Lorenz C. Hofbauer, Martina Rauner, and Sven Perner
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0301 basic medicine ,Cell type ,Bone Neoplasms ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Prostate ,Tumor Microenvironment ,medicine ,Animals ,Humans ,Molecular Targeted Therapy ,Neoplasm Metastasis ,business.industry ,Therapies, Investigational ,Bone metastasis ,Cell migration ,Neoplastic Cells, Circulating ,medicine.disease ,Haematopoiesis ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,Bone marrow ,Stem cell ,business - Abstract
Bone metastases are a frequent and severe complication of advanced-stage cancers. Breast and prostate cancers, the most common malignancies in women and men, respectively, have a particularly high propensity to metastasize to bone. Conceptually, circulating tumour cells (CTCs) in the bloodstream and disseminated tumour cells (DTCs) in the bone marrow provide a snapshot of the dissemination and colonization process en route to clinically apparent bone metastases. Many cell types that constitute the bone microenvironment, including osteoblasts, osteocytes, osteoclasts, adipocytes, endothelial cells, haematopoietic stem cells and immune cells, engage in a dialogue with tumour cells. Some of these cells modify tumour biology, while others are disrupted and out-competed by tumour cells, thus leading to distinct phases of tumour cell migration, dormancy and latency, and therapy resistance and progression to overt bone metastases. Several current bone-protective therapies act by interrupting these interactions, mainly by targeting tumour cell-osteoclast interactions. In this Review, we describe the functional roles of the bone microenvironment and its components in the initiation and propagation of skeletal metastases, outline the biology and clinical relevance of CTCs and DTCs, and discuss established and future therapeutic approaches that specifically target defined components of the bone microenvironment to prevent or treat skeletal metastases. more...
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- 2021
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31. Kinetic and Static Analysis of Poly-(Adenosine Diphosphate-Ribose) Polymerase-1–Targeted 18F-Fluorthanatrace PET Images of Ovarian Cancer
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Robert K. Doot, David A. Mankoff, Varsha Viswanath, Robert H. Mach, Michael D. Farwell, Fiona Simpkins, Daniel A. Pryma, Austin R. Pantel, Mehran Makvandi, Lilie L. Lin, Anthony J. Young, Hsiaoju Lee, Shihong Li, Tiffany Dominguez, and Erin K. Schubert more...
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Oncology ,education.field_of_study ,medicine.medical_specialty ,business.industry ,Population ,Cancer ,Venous blood ,medicine.disease ,medicine.anatomical_structure ,Pharmacokinetics ,Prostate ,Positron-Emission Tomography ,Internal medicine ,PARP inhibitor ,medicine ,Biomarker (medicine) ,Radiology, Nuclear Medicine and imaging ,Clinical Investigation ,education ,business ,Ovarian cancer - Abstract
The poly-(adenosine diphosphate-ribose) polymerase (PARP) family of proteins participates in numerous functions, most notably the DNA damage response. Cancer vulnerability to DNA damage has led to development of several PARP inhibitors (PARPi). This class of drugs has demonstrated therapeutic efficacy in ovarian, breast, and prostate cancers, but with variable response. Consequently, clinics need to select patients likely to benefit from these targeted therapies. In vivo imaging of (18)F-fluorthanatrace uptake has been shown to correspond to PARP-1 expression in tissue. This study characterized the pharmacokinetics of (18)F-fluorthanatrace and tested kinetic and static models to guide metric selection in future studies assessing (18)F-fluorthanatrace as a biomarker of response to PARPi therapy. Methods: Fourteen prospectively enrolled ovarian cancer patients were injected with (18)F-fluorthanatrace and imaged dynamically for 60 min after injection followed by up to 2 whole-body scans, with venous blood activity and metabolite measurements. SUV(max) and SUV(peak) were extracted from dynamic images and whole-body scans. Kinetic parameter estimates and SUVs were assessed for correlations with tissue PARP-1 immunofluorescence (n = 7). Simulations of population kinetic parameters enabled estimation of measurement bias and precision in parameter estimates. Results: (18)F-fluorthanatrace blood clearance was variable, but labeled metabolite profiles were similar across patients, supporting use of a population parent fraction curve. The total distribution volume from a reversible 2-tissue-compartment model and Logan reference tissue distribution volume ratio (DVR) from the first hour of PET acquisition correlated with tumor PARP-1 expression by immunofluorescence (r = 0.76 and 0.83, respectively; P < 0.05). DVR bias and precision estimates were 6.4% and 29.1%, respectively. SUV(max) and SUV(peak) acquired from images with midpoints of 57.5, 110 ± 3, and 199 ± 4 min highly correlated with PARP-1 expression (mean ± SD, r ≥ 0.79; P < 0.05). Conclusion: Tumor SUV(max) and SUV(peak) at 55–60 min after injection and later and DVR from at least 60 min appear to be robust noninvasive measures of PARP-1 binding. (18)F-fluorthanatrace uptake in ovarian cancer was best described by models of reversible binding. However, pharmacokinetic patterns of tracer uptake were somewhat variable, especially at later time points. more...
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- 2021
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32. DElayed COloRectal cancer care during COVID-19 Pandemic (DECOR-19): Global perspective from an international survey
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Santoro, Giulio A., Grossi, Ugo, Murad-Regadas, Sthela, Nunoo-Mensah, Joseph W., Mellgren, Anders, Di Tanna, Gian Luca, Gallo, Gaetano, Tsang, Charles, Wexner, Steven D, LA TORRE, Filippo, Abary Ryan Rainiel, A, Philippines, Abdelwahab Khaled M, Egypt, Abellán Antonio M, Spain, Abraham Ned, Australia, Achkasov Sergey I, Russia, Adamina Michel, Switzerland, Adamo Vincenzo, Italy, Agapov Mikhail, Russia, Agarwal Amit, Usa, Aguado López Héctor, Spain, Aguilar Werner, Chile, AguilarMartínez María Del Mar AM, Spain, Aguilera Asuncion, Spain, Ahmed Jamil, Uk, Aiello Domenico, Italy, Akagi Tomonori, Japan, Akcakaya Adem, Turkey, Akhtar Khalid I, Pakistan, Akiba Ricardo, Brazil, Akrami Majid, Iran, Akyol Cihangir, Turkey, Alaamer Ohood H, Saudi Arabia, Alapati Kishore, India, Alasari Sami, Saudi Arabia, Albastaki Sara, Uae, Albergaria Diogo, Portugal, Alconchel Felipe, Spain, Alerta-Torre Andrea J, Philippines, Alex Ochsner, Switzerland, Alexander Herold, Germany, Alfaro Samuel, El Salvador, Ali Jehangir F, Pakistan, Aliyazicioglu Tolga, Turkey, Almgla Naser, South Africa, Alonsopoza Alfredo, Spain, Al-Radjid Jamiri, Philippines, Alselaim Nahar A, Saudi Arabia, Altaf Kiran K, Uk, Althebaity Rasha, Saudi Arabia, Altinel Yuksel, Turkey, Altiparmak Basak, Turkey, Altomare Donato F, Italy, Alvandipour Mina, Iran, Alvarez-Gallego Mario, Spain, Alyami Mohammad, Saudi Arabia, Amado Sandra, Portugal, Amato Antonio, Italy, Amodio Pietro M, Italy, Ana-Maria Mușină, Romania, Andrade Luis, Chile, Andreas Kohler, Switzerland, Angelini Giulio, Italy, Angenete Eva, Sweden, Annicchiarico Alfredo, Italy, Antelo Galarza Renan, Bolivia, Anwer Mariyah, Pakistan, Aparício David J, Portugal, Arciniega Jose A, Mexico, Arezzo Alberto, Italy, Argenio Giulio, Italy, Arenas Mara, Belgium, Arnaud Alves AA, France, Arredondo Jorge, Spain, Arslan Baha, Turkey, Arya Shobhit, Uk, Aselmann Heiko, Germany, Aumann Georg, Germany, Avanzolini Andrea, Italy, Avendano Rodolfo, Chile, Awedew Atalel F, Ethiopia, Ayantunde Abraham, Uk, Aycan Ilker, Turkey, Aytac Erman, Turkey, Azevedo Constança TM, Portugal, Ba Am, Iraq, Bader Fg, Germany, Baehrle Markus, Germany, Bagaglini Giulia, Italy, Balaban Vladimir, Russia, Balciscueta Zutoia, Spain, Balciscueta Izaskun, Spain, Baldazzi Gianandrea, Italy, Balik Emre, Turkey, Bandolon Robert, Philippines, Barberis Andrea, Italy, Barisic Goran I, Serbia, Barrera Alejandro, Chile, Barros Inês MSF, Portugal, Basaran Betul, Turkey, Basilio Pedro C, Brazil, Bech Flemming, Denmark, Behboo Roubik, Iran, Behboudi Behnam, Iran, Beitia Ivan E, Panama, Bellato Vittoria, Italy, Bellolio Felipe, Chile, Benli Sami, Turkey, Bernal Jc, Spain, Bernante Paolo, Italy, Berrospi Francisco E, Peru, Bertelson Noelle, Usa, Bevan Katharine, Uk, Bhama Anuradha, Usa, Bianco Francesco, Italy, Bievel Radulescu Raluca, Romania, Bintraiki Thamer, Saudi Arabia, Bisgin Tayfun, Turkey, Bislenghi Gabriele, Belgium, Blaslaina Juanluis, Spain, Bloom Itm, Uk, Boehm Gabriele, Germany, Bogoni Selene, Italy, Bohlooli Mehrdad, Iran, Bondurri Andrea, Italy, Boni Luigi, Italy, Bonomi Alessandro Michele, Italy, Booning Nitikun, Thailand, Boonpipattanapong Teeranut, Thailand, Bordeianou Liliana, Usa, Bossard Kerrie, Usa, Botelho Maria, Portugal, Boto Carlos, Portugal, Bottini Corrado, Italy, Bouchagier Konstantinos, Greece, Boutall Adam, South Africa, Bowers Dan, Usa, Bozbiyik Osman, Turkey, Brambilla Eduardo, Brazil, Brisinda Giuseppe, Italy, Brizzi Maria Pia, Italy, Brizzolari Marco, Italy, Brusciano Luigi, Italy, Bucci Luigi, Italy, Buchwald Pam, Sweden, Bugra Dursun, Turkey, Bui Andrew, Australia, Buldanlı Mehmet Zeki, Turkey, Bulut Orhan, Denmark, Cagigas Fernandez Carmen, Spain, Cai Yuankun, China, Calcerrada Alises Enrique, Spain, Caldes Pedro, Portugal, Calussi Marco, Italy, Calvo Espino Pablo, Spain, Campanelli Michela, Italy, Campbell Ken, Uk, Campennì Paola, Italy, Canda Arasemre, Turkey, Capolupo Gabriella T, Italy, Caravana Jorge, Portugal, Carballo Federico HE, Argentina, Carbone Fabio, Italy, Carcamo Leonardo C, Chile, Cardoso Paulo, Portugal, Cariati Maria, Italy, Caricato Marco, Italy, Carmona Maria, Spain, Carpelan Holmstrom Monika, Finland, Carrié Augusto J, Argentina, Carrino Francesco, Italy, Cartucho Daniel DF, Portugal, Carvalho Marcia, Portugal, Carvas João M, Portugal, Casagranda Biagio, Italy, Casimiro Carlos, Portugal, Castro Anyely, Dominican Republic, Catiwala-An Michael T, Philippines, Caushaj Philip F, Usa, Cavallo Debora, Italy, Cedermas Mariela, Argentina, Celayir Fevzi, Turkey, Celentano Valerio, Uk, Cengiz Fevzi, Turkey, Chaisomboon Nopdanai, Thailand, Chenghua Luo, China, Cherepenin Mikhail, Russia, Chessa Antonella, Italy, Chierici Andrea, France, Chok Aikyong, Singapore, Chouliaras Christos, Greece, Chowchankit Irin, Thailand, Christou Niki, France, Chun Hokyung, South Korea, Cillara Nicola, Italy, Cinza Margarida, Portugal, Cione Gianpiero, Italy, Cipe Gokhan, Turkey, Ciprian Duta, Romania, Cirocco William, Usa, Citgez Bulent, Turkey, Clark Jill E, Usa, Clementi Ilaria IC, Italy, Clerc Daniel, Switzerland, Clermonts Journal Pre-proof 39 Stefan HEM, Netherlands, Cobellis Luigi, Italy, Colak Tahsin, Turkey, Colao Garcia Laura, Spain, Colombo Francesco, Italy, Comba Andrea, Italy, Coret Franco Alba CFA, Spain, Correa Bonito Alba, Spain, Cosman Bard, Usa, Costa Susana GS, Portugal, Costa Marta RP, Portugal, Costa Pereira Joaquim, Portugal, Cózar Lozano Coral, Spain, Cravero Francesca, Italy, Creavin Ben, Ireland, Cross Katie LR, Uk, Cruz Arturo, Spain, Cui Junhui, China, Cunha Miguel F, Portugal, Curado Antonio, Portugal, D'Ugo Stefano, Italy, Dajti Irida, Albania, Dalessandro Antonio, France, Dal Monte Giorgio, Italy, Danelli Piergiorgio, Italy, Daniels Ian R, Uk, Dar Asif M, India, Davies Richard J, Uk, De Andrés Beatriz, Spain, De Angelis Marsilio, Italy, De Falco Nadia, Italy, De Luca Maurizio, Italy, De Luca Raffaele, Italy, De Nardi Paola, Italy, De Rosa Michele, Italy, De Silva Kaluthanthiri Patabanadi VR, Sri Lanka, De Simone Veronica, Italy, De Wilt Johannes HW, Netherlands, De-León-Rendón Jorge Luis, Mexico, Dean Phillip, Usa, Deangelis Nicola, France, Dedemadi Georgia, Greece, Delgadillo Xavier, Switzerland, Delgadillo Edgar, Switzerland, D’Elia Antonio, Italy, Delibegovic Samir, Bosnia and Herzegovina, Delis S, Greece, Della Porta Massimiliano, Italy, Del Rio Paolo, Italy, De Marano Gaetano, Italy, Demey Karel, Belgium, Demirli Atıcı Semra, Turkey, Denoya Paula I, Usa, Derebey Murat, Turkey, De Santis Mariangela, France, Devezas Vítor BS, Portugal, Dhaif Ali, Bahrain, Diaconescu Bogdan, Romania, Di Candido Francesca, Italy, Die Javier, Spain, Dieguez Beatriz, Spain, Dieter Hahnloser, Switzerland, Diez Alonso Manuel, Spain, Dimaren Ishmael, Philippines, Disimone Massimo, Italy, Doerner Johannes, Germany, Domingos Hugo VG, Portugal, Dominguez Rubén RD, Paraguay, Dorenbusch Michael, Usa, Doulias Triantafyllos A, Uk, Duff Sarah, Uk, Dulskas Audrius, Lithuania, Dunn Gary, Usa, Duque-Mallén Victoria, Spain, Dusek Tomas, Czech Republic, Dusitanond Navara, Thailand, Dzulkarnaen Zakaria Andee, Malaysia, Dworkin Michael, United Kingdom, Dybau Aleh, Belarus, Dziakova Jana, Spain, Dziki Lukasz, Poland, Dziki Adam, Poland, Efetov Sergey K, Russia, Eisa Mohamed, Egypt, Eisenstat Ted, Usa, El Sorogy Mohamed, Egypt, El-Hussuna Alaa, Denmark, Elfeki Hossam, Egypt, Elhussuna Alaa, Denmark, Eliasrabelo Fernanda, Brazil, Ellis Tyler, Usa, Elzalabany Tamer, Egypt, Emile Sameh H, Egypt, Emiroglu Mustafa, Turkey, Emmanuel Odet, France, Enomoto Masanobu, Japan, Epifani Angelo Gabriele, Italy, Erenler Ilknur, Turkey, Erkan Arman, Usa, Erol Timuçin, Turkey, Erturk Suphan, Turkey, Escalante Ricardo, Venezuela, Escartin Jorg, Spain, Escrevente Ricardo, Portugal, Espin-Basany Eloy, Spain, Estaire-Gomez Mercedes, Spain, Falaschi Federica, Italy, Falken Ylva, Sweden, Fantini Corrado, Italy, Fantozzi Mauricio, Argentina, Farid Asim, Usa, Farina Pablo, Argentina, Farmer Russ, Usa, Farmer Martin, Uk, Faul Eleanor M, Ireland, Favara Andrea, Italy, Febra Pedro, Portugal, Fenner Lyra Junior Humberto, Brazil, Fermani Claudio, Argentina, Fernandes Fábio FN, Portugal, Fernandes Miguel, Portugal, Ferracci Federica, Italy, Ferrara Francesco, Italy, Ferrari Giovanni, Italy, Ferrario Luca, Italy, Ferreira Rita, Portugal, Ferreira Carlos, Portugal, Ferris Jeff, Usa, Ferronetti Antonio, Italy, Fialho Guilherme L, Portugal, Fichera Alessandro, Usa, Figueiredo Odete, Portugal, Filipe Vieira Pedro JG, Portugal, Fiore Felicia, Italy, Folliero Cristina, Italy, Folstad Torbjorn, Norway, Forerotorres Alexander, Spain, Forgan Timothy R, South Africa, Franceschilli Marzia, Italy, Frizelle Frank, New Zealand, Froehner Junior Ilario, Brazil, Frois Miguel, Portugal, Frontali Alice, France, Fu Chuangang, China, Fulginiti Serena, Italy, Galiffa Giampaolo, Italy, Gallagher Hugh J, Uk, Gallardo Cristian, Chile, Galleano Raffaele, Italy, Gama Barbara, Portugal, Garcia Conde Maria, Spain, Garcia Granero Alvaro, Spain, Garcia Esther, Spain, García Sánchez Felipe, Spain, Garcia Septiem Javier, Spain, Garcia Walter, Argentina, Garcia-Urena Miguel Angel, Spain, Garmanova Tatiana N, Russia, Garofalo Thomas, Usa, Garoufalia Zoe, Greece, Garulli Gianluca, Italy, Gatti Matteo, Italy, Gecim Ethem, Turkey, Gellona Jose, Chile, Gercek Yuksel, Uk, Ghignone Federico, Italy, Gianchandani Moorjani Rajesh, Spain, Gianfrancisco James A, Usa, Giani Iacopo, Italy, Gibert Juan, Spain, Gilles Manceau, France, Gilmore Andrew, Australia, Gilsanz Carlos, Spain, Gilshtein Hayim, Usa, Girgin Behic, Turkey, Giria Joao, Portugal, Giuffrida Maria Carmela, Italy, Giuliani Antonio, Italy, Goi Gloria, Italy, Golovina Anastasiya, Russia, Gomez Rosado Juan Carlos, Spain, González Enrique, Spain, Granada Nemesio, Philippines, Grimme Frederike, Netherlands, Grobler Stephen, South Africa, Guaitoli Eleonora, Italy, Guerci Claudio, Italy, Guerra Daniel, Mexico, Guerreiro José MM, Portugal, Guido Jutten, Belgium, Gulcu Baris, Turkey, Gunay Emre, Turkey, Gundes Ebubekir, Turkey, Gurbuz Bulent, Turkey, Gurjar Shashank, Uk, Hainsworth Alison J, Uk, Hall Nigel, Uk, Hamed Hosam H, Egypt, Hammer Clare, Uk, Hannon Rob, Ireland, Harmston Christopher, New Zealand, Harran Nadine, South Africa, Hartendorp Paul, Usa, Hassan Iyad, Uae, Hassan Imran, Usa, Hawkins Alexander T, Usa, Hayssen Theresa, Usa, Hendren Samantha, Usa, Hernandez Garcia Miguel, Spain, Hershman Michael, Journal Pre-proof 40 UK, Hild Stefanie, Germany, Hilton Joanna, Uk, Hiranyakas Art, Thailand, Ho Ming, Australia, Hollington Paul, Australia, Holubar Stefan, Usa, Hompes Roel, Netherlands, Houcine Maghrebi, Tunisia, Hovsepyan Vardges, Armenia, Hul Rene, Netherlands, Hunt Louise E, Uk, Hyder Zargham, Uk, Ibrahim Aini F, Malaysia, Iglesias Gustavo, Brazil, Iesalnieks Igors, Germany, Ilkanich Andrei, Russia, Imanova Nargiz, Azerbaijan, Isik Arda, Turkey, Jayathilaka Buddika, Uk, Jimenez Virginia, Spain, Jimenez-Gomez Luis Miguel, Spain, Jitmungngan Romyen, Thailand, Joelsson Magnus, Sweden, Joshi Heman, Uk, Juloski Jovan T, Serbia, Juwid Abdallah E, Libya, Kanjanasilp Prapon, Thailand, Kannappa Lava, Uk, Kanno Danilo, Brazil, Kaplan Esin, Turkey, Kara Yasin, Turkey, Kartal Abdulcabbar, Turkey, Kawamura Junichiro, Japan, Kaya Tayfun, Turkey, Kazemi Nava Andrea, Italy, Kazachenko Ekaterina A, Russia, Kelkar Ashish, Uk, Kelly Michael E, Ireland, Keramati Mohammad Reza, Iran, Kerawala Asad, Pakistan, Khalil Mohammad I, Bangladesh, Khan Jim S, Uk, Khan Rbn, Uk, Khitaryan Alexander, Russia, Kinjo Tatsuya, Japan, Kirilova Tanya N, Bulgaria, Kirmizi Yasemin, Turkey, Klaristenfeld Daniel, Usa, Knapp Jens, Norway, Koc Mehmet A, Turkey, Kocián Petr, Czechia, Konishi Tsuyoshi, Japan, Konstantoudakis Georgios, Cyprus, Konsten Joop, Netherlands, Kontovounisios Christos, Uk, Korkmaztoker Melike, Turkey, Kørner, Hartwig, Norway, Krdzic Igor, D, Serbia, Krivokapic Zoran, Serbia, Kumar Sanjeev, India, Kumar Sandip, Malaysia, Kushtrim Shala, Germany, Kynaston James, Uk, Langmayr Johannes, Austria, La Torre Marco, Italy, La Torre Filippo, Italy, Labalde Maria, Spain, Lagopoulos Vasileios, Greece, Lal Roshan, Uk, Landaluce- Olavarria Aitor, Spain, Langone Antonio, Italy, Lapolla Pierfrancesco, Italy, Larach Sergio, Usa, Larach, Andres, Chile, Larsson, Peranders, Sweden, Lasala Alfred, Philippines, Lauretta Andrea, Italy, Leao Pedro, Portugal, Lee Pamela C, Usa, Lee Suk-Hwan, South Korea, Lee Wooyong, South Korea, Lefevre Jeremie H, France, Leite Julio, Portugal, Lemaire Julien, Belgium, Lemma Maria, Italy, Lemme Gustavo Nestor, Argentina, Lenna Giovanni, Italy, Leo Cosimo Alex, Uk, Leventoglu Sezai, Turkey, Licardie Eugenio, Spain, Lienert Mark, Germany, Lima Sergio, Brazil, Limbert Manuel CSB, Portugal, Lisi Giorgio, Italy, Litta Francesco, Italy, Littaua Dennis, Philippines, Liu Fanlong, China, Liyanage Chris, New Zealand, Llovera Antony, Cuba, Lo Oswens, China, Lo Dico Rea, France, Lobascio Pierluigi, Italy, Lohsiriwat Varut, Thailand, Lombana Luis, Colombia, Lopez Marc, Philippines, Lopez Jose, Mexico, Lopez Francisco, Chile, Lorber Julie, Usa, Losada Manuel, Spain, Lowenfeld Lea, Usa, Lucci Enrico, Italy, Luglio Gaetano, Italy, Lynch Craig, Australia, Luqman, Pakistan, Machairas Nikolaos, Uk, Maciel João MRP, Portugal, Madbouly Khaled, Egypt, Madhoun, Nisreen, Usa, Maffioli, Anna, Italy, Magbojos Christian Raymond S, Philippines, Magistro Carmelo CM, Italy, Magrino Thomas, Usa, Makhoul Rami, Usa, Mallmann Karen DP, Brazil, Manatakis Dimitrios K, Greece, Mancini Stefano, Italy, Manfredelli Simone, France, Mangione John, Usa, Manso Antonio, Portugal, Marakutsa Eugen V, Moldova, Marano Alessandra, Italy, Marchesi Federico, Italy, Marchiori Mauro, Brazil, Marfan Michael, Australia, Marianelli Raphael, Brazil, Mariani Nicolò M, Italy, Marimuthu Kalimuthu, Uk, Marinello Franco, Spain, Marinis Athanasios, Greece, Marino Marco V, Italy, Markides Georgios, Cyprus, Marquez Lucila, Spain, Marra Angelo A, Italy, Martín Navarro Fabian, Mexico, Martin-Martin Gonzalo P, Spain, Martinez Javier, Spain, Martinez-Iglesias Marta A, Uk, Martins Ruben AFP, Portugal, Martins Ana RG, Portugal, Mascali Davide DM, Italy, Massucco Paolo, Italy, Matas Fernando, Spain, Mathew Alexander, Usa, Matzel Klaus E, Germany, Maun Dipen, Usa, Maurus Christine F, Switzerland, McCormick Jim, Usa, McIntyre Robert, Uk, McKinley Aileen, Uk, McLemore Lisa, Usa, McNeil Jennifer, Usa, McNevin Shane, Usa, Medich David, Usa, Medina Cesar, Mexico, Medina Quintana Rita E, Spain, Melo Ingrid, Paraguay, Melstrom Kurt A, Usa, Mendoza-Moreno Fernando, Spain, Menna Maria Paola, Italy, Mentz Ricardo, Argentina, Merlini David A, Italy, Mihmanli Mehmet, Turkey, Mike Spencer, Usa, Millan Monica, Spain, Miller Jerad, Usa, Milone Marco, Italy, Minahi Ilyas, Uk, Minaya-Bravo Ana María, Spain, Mingoli Andrea, Italy, Minicozzi Annamaria, Uk, Miranda Pedro, Portugal, Miro Antonio, Italy, Miskovic Danilo, Uk, Mistrangelo Massimiliano, Italy, Mitra Rajarshi, Uae, Mittal Rohin, India, Mladenovikj Dragoslav P, North Macedonia, Moctezuma Velázquez Paulina, Mexico, Mohamed Kamil Nil Amri, Malaysia, Mohammed Mohammed MH, Egypt, Mohsen Yasser MA, Uk, Monami Benoit N, Belgium, Monroe Justin, Usa, Monroy Hermogenes DJ, Philippines, Montori Giulia, Italy, Montuori Mauro, Italy, Mora-Guzmán Ismael, Spain, Moraes Ana, Brazil, Morales Carlos, Usa, Morelli Luca, Italy, Moreno Almudena, Spain, Moretto Gianluigi, Italy, Morici Riccardo, Italy, Morini Andrea, Italy, Moro-Valdezate David, Spain, Moroni Eliana, Italy, Morton Dion, Uk, Moura Catarina, Portugal, Moysidis Moysis M, Greece, Mozo Ana S, Spain, Nacion Aeris Jane D, Philippines, Nada Mohamed, Journal Pre-proof 41 Egypt, Nagasaki Toshiya, Japan, Nakamoto Yoshihiko, Japan, Neary Peter, Ireland, Negoi Ionut, Romania, Neijenhuis Peter A, Niger, Ng Simon SM, China, Niazi Samiullah, Pakistan, Nikoupour Hamed, Iran, Nogueiro Jorge PM, Portugal, Noguera Jose, Spain, Nova Carlos, Portugal, Nunes Amadeu, Portugal, O'Riordain Micheal G, Ireland, Oke Olatunbosun A, Nigeria, Okkabaz Nuri, Turkey, Oliva Cristiano, Italy, Oliveira Olga, Portugal, Oliveira Manuel, Portugal, Oliveira Antonio, Portugal, Oliveira Lucia CC, Brazil, Olivier James B, Uk, Olivier Pittet, Switzerland, Omejc Mirko, Slovenia, Ong Loreto B, Philippines, Ong David, Malaysia, Onglao Mark, Philippines, Onody Peter, Hungary, Orefice Raffaele, Italy, Ortega David, Peru, Ozben Volkan, Turkey, Ozcan Onder, Turkey, Ozturk Ersin, Turkey, Pacheco Andre, Portugal, Paci Marco, France, Paczosa Marcin, Poland, Padmanabhan Anantha, Usa, Pai Ajit, India, Palmer Gabriella, Sweden, Pandey Diwakar, India, Panis Yves, France, Pantel, Haddon, Paonariang Krisada, Thailand, Papa Mario V, Italy, Papadopoulos Aristeidis, Greece, Papagni Vincenzo, Italy, Papp Andras, Sweden, Parello Angelo, Italy, Parente Alessandro, Uk, Parra Pedro, Spain, PascualMigueláñez Isabel, Spain, Pata Francesco, Italy, Patel Nikhil, Usa, Patel Reeya, Uk, Pattyn Paul RL, Belgium, Paul Bikram, Usa, Pavanello Maurizio, Italy, Pedro Luis E, Argentina, Pellino Gianluca, Spain, Peltrini Roberto, Italy, Peña Ros Emilio, Spain, Pennacchi Luca UC, Italy, Pereira André, A Portugal, Pereira Bela, Portugal, Perez Guillermo, Ecuador, Perez Horacio, Portugal, Perez Natalia, Spain, Perez Flecha Marina, Spain, Perinotti Roberto, Italy, Pernazza Graziano, Italy, Perra Teresa, Italy, Pertile Davide, Italy, Pessia Beatrice, Italy, Pessoa Joana, Brazil, Petagna Lorenzo, Italy, Peters Walter, Usa, Petit Mindy, Usa, Petracca Gabriele Luciano, Italy, Pezzolla Francesco, Italy, Philp Matthew, Usa, Pianim Nana, Usa, Picciariello Arcangelo, Italy, Piccinini Pablo E, Argentina, Piccinni Giuseppe, Italy, Piccolo Davide, Italy, Pigalarga, Rodolfo, Pikarsky Alon J, Israel, Pimentel Alice, Portugal, Pinchot Scott, Usa, Pinotti Enrico, Italy, Pinto Diogo, Portugal, Pirozzi Felice, Italy, Plastiras Aris, Greece, Platto Marco, Italy, Plerhoples Tim, Usa, Podda Mauro, Italy, Poggi Luis, Peru, Polastri Roberto, Italy, Porcu Alberto, Italy, Porter Michael, Usa, Poskus Eligijus, Lithuania, Potolicchio Analia I, Argentina, Poylin Vitaliy, Usa, Pozzo Mauro, Italy, Pramateftakis Manos, Greece, Pravosudov Igor V, Russia, Praxedes Vanessa P, Portugal, Primoromaguera Vicent, Spain, Progno Valerio C, Italy, Proud David M, Australia, Pucciarelli Salvatore, Italy, Qadir Abdul, Uk, Qayoom Hina, Pakistan, Quindos Patricia, Spain, Quintanilha Rui, Portugal, Quinteros Francisco A, Usa, Qureshi Nafees, Uk, Rachadell Juan J, Portugal, Ralf Schmidt, Germany, Raman Shankar, Usa, Ramos Diego, Spain, Ramos Jose, Portugal, Ramwell, Andrew, Randazzo, Valentina, Rattanarpichart Patsaporn, Thailand, Ratto Carlo, Italy, Rautio Tero, Finland, Raviolo Carla, Italy, Read Thomas, Usa, Real Joao, Portugal, Rega Daniela, Italy, Regadas Francisco, Brazil, Regenbogen Scott, Usa, Reia Marta, Portugal, Reina Angel, Spain, Rems Miran, Slovenia, Rencuzogullari Ahmet, Turkey, Renwick Andrew A, Uk, Reyes Juan C, Colombia, Reyes Jeryl Anne Silvia R, Philippines, Ribeiro Jr Ulysses, Brazil, Ridzuan Farouk, Singapore, Ripetti Valter, Italy, Ripoll Cristina, Mexico, Ripollés-Melchor Javier, Spain, Rizal Rizal, Indonesia, Rizk Mariam, Uk, Rizvi Irfan, Usa, Robinson Jonathan, Uk, Rodimov Sergei, Russia, Rodrigues João VL, Brazil, Rodriguez Javier, Mexico, Rodriguez Cristian, Argentina, Rodriguez Homero, Panama, Rodriguez Garcia Jaime, Mexico, Roig Jose, Spain, Rojanasakul Arun, Thailand, Rojas Julio, Chile, Romanelli Elena, France, Rosa Fausto, Italy, Rosato Guillermo, Argentina, Rosenberg Robert, Switzerland, Rosete Manuel, Portugal, Roslani April C, Malaysia, Rottoli Matteo, Italy, Roxas Manuel Francisco Roxas T, Philippines, Roxburgh Campbell S, Uk, Ruan Joseph, Usa, Rubbini Michele M, Italy, Rubio Eduardo, Spain, Ruddy Theresa, Usa, Rueda Camilo, Spain, Ruiztovar Jaime, Spain, Rusconi Andrea, Italy, Rutegård Martin, Sweden, Sá Milene RRM, Portugal, Saad Luiz Henrique Cury, Brazil, Sadien Iannish D, Uk, Sadowski Brian M, Usa, Saeed Mirza Faraz, Bahrain, Safiyeva Aynur K, Azerbaijan, Sagap Ismail, Malaysia, Sahnan Kapil, Uk, Sairafi Rami, Saudi Arabia, Saklami Avanish P, India, Salgado-Nesme Noel NSN, Mexico, Salman Nevriye, Turkey, Samalavicius Narimantas E, Lithuania, Sambucci Daniele, Italy, Sanchez Noel, Usa, Sanchez Robles Juan Carlos, Mexico, Sanmiguel Carlos, Spain, Santacruz Eduardo, Paraguay, Santoni Simone, Italy, Santos Pedro MD, Portugal, Santos Brian U, Argentina, Santos Carlos, Portugal, Sapienza Paolo, Italy, Saracoglu Ayten, Turkey, Saracoglu Kemal T, Turkey, Sardinas Carlos, Venezuela, Sari Ramazan, Turkey, Sarma Diwakar, Uk, Sartori Alberto A, Italy, Sasia Diego, Italy, Sbaih Mohammed H, Saudi Arabia, Scabini Stefano, Italy, Scaringi Stefano, Italy, Scheinin Tom M, Finland, Schiavo Marcello, Italy, Schizas Alexis, Uk, Sciaudone Guido, Italy, Scognamillo Fabrizio, Italy, Scott Kelley, Usa, Scow Jeffrey S, Usa, Sechi Raffaele, Italy, Seehra Harkiran, Uk, Segering Joerg, Germany, Selcuk Mehtap, Turkey, Journal Pre-proof 42 Selemane Carlos, Mozambique, Seltman Ann, Usa, Selvaggi Francesco, Italy, Sensi Bruno, Italy, SeowChoen Francis, Singapore, Sernagiotto Carlo, Italy, Serralta De Colsa Daniel, Spain, Serrano González Javier, Spain, Sert Ismail, Turkey, Serventi Alberto, Italy, Sforza Sergio, Italy, Shabbir Jamshed, Uk, Shabeeb Fadel, Uae, Shafik Ali, Egypt, Shalaby Mostafa, Egypt, Shanker Bethann, Usa, Shanmugam Venkatesh, Uk, Shariff Umar, Uk, Shehta Ahmed, Egypt, Shelton Andrew, Usa, Shintaro Akamoto, Japan, Shlyk Daria, Russia, Shukla Amit, Uk, Sibio Simone, Italy, Sietze Koopal, Netherlands, Sigurdardottir Johanna, Sweden, Silva Jorge, Mexico, Silva Anaisa, Portugal, Simianu Val, Usa, Singh Baljit, Uk, Siragusa Leandro, Italy, Sirikurnpiboon Siripong, Thailand, Sivrikoz Emre, Turkey, Sizonenko Nikolay, Russia, Slavchev Mihail T, Bulgaria, Sniuolis Pranas, Lithuania, Soares Duarte, Qatar, Sojar Valentin, Slovenia, Sokmen Selman, Turkey, Sokol Thomas, Usa, Soldatov Denis, Russia, Soncini Stefania, Italy, Sordo Ricardo, Mexico, Sosa María V, Spain, Sousa Xavier, Portugal, Sozutek Alper, Turkey, Spiezio Giovanni, Italy, Spinelli Antonino, Italy, Stahl Etienne, Mexico, Stanojevic Goran Z, Serbia, Steckel Brian, Usa, Stefan Neagu, Romania, Stefanescu Victor, Romania, Steinhagen Randolph, Usa, Stella Marco, Italy, Stephensen Bree D, Australia, Stevenson Andrew RL, Australia, Stitzenberg Karyn, Usa, Strombom Paul, Usa, Sturiale Alessandro, Italy, Suhail Anjum, Pakistan, Sungurtekin Ugur, Turkey, Sutton Jeffrey M, Usa, Suwannakij Chanchai, Thailand, Szczepkowski Marek, Poland, Sztipits Tamas, Hungary, Takashi Akiyoshi, Japan, Takkenberg Marijn, Netherlands, Tallon-Aguilar Luis, Spain, Tam Michael, Usa, Tamburini Andrea M, Italy, Tamini Nicolò, Italy, Tammaro Pasquale, Italy, Tan Kerkan, Singapore, Tan Teerasan, Thailand, Tanal Mert, Turkey, Tanda Cinzia, Italy, Tang Jinghua, China, Tapiolas Ingrid, Uk, Täreby Magnus, Sweden, Tariverdiev Andrey, Russia, Tayar Serkan, Turkey, Tejedor Patricia, Spain, Terrosu Giovanni, Italy, Testa Alessandro, Italy, Tewari Shirish, Uk, Thabet Waleed, Egypt, Thakur Sukesh, India, Thomas Ehmann, Germany, Thomas Kuruc, Germany, Tiesi Vincenzo, Italy, Tin Moemoetin, Myanmar, Tita Agustin C, Argentina, Titu Liviu V, Uk, Tkachenko Fedot, Ukraine, Tonello Paolo, Italy, Tooley Richard, Usa, Torres Juan, Spain, Troci Albert, Italy, Trompetto Mario, Italy, Troncoso Pereira Paula, Spain, Tropeano Francesca Paola FP, Italy, Trostchansky Ivan, Uruguay, Tsujinaka Shingo, Japan, Tufo Andrea, Italy, Tulina Inna, Russia, Turati Luca, Italy, Turchina Catalin, Sweden, Turina Matthias, Switzerland, Tutino Roberta, Italy, Tyler Km, Usa, Uemura Mamoru, Japan, Unal Ayse G, Turkey, Uraiqat Ahmad, Jordan, Uribe Sebastián, Chile, V Duke, Usa, Vailati Bruna, Brazil, Vaingurt Mariano, Argentina, Valente Michael, Usa, Van Dellen Jonathan, Uk, Van Ramshorst Gabrielle H, Belgium, Vannelli Alberto, Italy, Vanriel W, Belgium, Varabei Aliaksandr, Belarus, Varcada Massimo, Uk, Varela Cristopher L, Venezuela, Varma Madhulika G, Usa, Vasapollo Leoluca F, Italy, Venn Mary L, Uk, Vercillo Kristin, Usa, Vergara-Fernandez Omar, Mexico, Veronesi Paolo, Italy, Vicente Aline, Brazil, Victor Tomulescu, Romania, Vieiradesousa Paulo, Portugal, Vignali Andrea, Italy, Vigorita Vincenzo, Spain, Vilchis Jose, Mexico, Villaverde Kathia, Peru, Vindevoghel Koen, Belgium, Violante Tommaso, Italy, Vitoopinyoparb Kasidin, Thailand, Voutsarakis Athanasios, Uk, Wainstein Ricardo, Argentina, Wakefield Simon, Uk, Wallon Conny, Sweden, Wang Yongbing, China, Wang Xiaodong, China, Wang Xiaofeng, China, Warden Claire, South Africa, Wei Rockson, China, Wheeler Matthew, Usa, Willem Bemelman, Netherlands, Wilson Matthew, Usa, Winter Des C, Ireland, Wongwiwatseree Yongsun, Thailand, Woon Kyung Jeong, South Korea, Wright Danette B, Australia, Wu Jiong, China, Wuraola Funmilola O, Nigeria, Xenaki Sofia A, Greece, Xiaohua Jiang, China, Xiaoqiang Jia, China, Xue Yahong, China, Xynos Evangelos, Greece, Yamada Kazunosuke, Japan, Yanar Hakan, Turkey, Yang Bolin, China, Yanishev Alexey, Russia, Yildirim Ali C, Turkey, Yildiz Ufukmete, Turkey, Yildiz Alp, Turkey, Yilmaz Mehmet, Turkey, Younis Muhammad Umar MUY, Uae, Yousef Zeyad, Saudi Arabia, Yu Dongsheng, China, Zalucki James, Usa, Zaman Ahamaduz, Bangladesh, Zamora Aída T, Spain, Zampitis Nikolaos, Cyprus, Zanus Giacomo, Italy, Zapata Gonzalo H, Argentina, Zelic Marko, Croatia, Zenger Serkan, Turkey, Zheng Jianyong, China, Zigiotto Daniele, Italy, Zmora Oded, Israel, Zoikas Athanasios, Greece, Zorcolo Luigi, Italy, Zucchella Martino, Italy, Zuhdy, Mohammad, Santoro G.A., Grossi U., Murad-Regadas S., Nunoo-Mensah J.W., Mellgren A., Di Tanna G.L., Gallo G., Tsang C., Rottoli M., and Wexner S.D. more...
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Male ,medicine.medical_specialty ,Delayed Diagnosis ,Internationality ,Colorectal cancer ,colorectal surgery - COVID-19 - delay - treatment - outcomes ,MEDLINE ,colorectal cancer ,030230 surgery ,medicine.disease_cause ,Article ,Time-to-Treatment ,03 medical and health sciences ,0302 clinical medicine ,Surveys and Questionnaires ,Pandemic ,medicine ,Humans ,Practice Patterns, Physicians' ,Elective surgery ,Personal protective equipment ,SARS-CoV-2 ,COVID-19 ,delayed surgery ,Coronavirus ,Infection Control ,business.industry ,Outbreak ,medicine.disease ,030220 oncology & carcinogenesis ,Preparedness ,Emergency medicine ,Female ,Surgery ,Colorectal Neoplasms ,business ,Colorectal Surgery - Abstract
Background The widespread nature of coronavirus disease 2019 (COVID-19) has been unprecedented. We sought to analyze its global impact with a survey on colorectal cancer (CRC) care during the pandemic. Methods The impact of COVID-19 on preoperative assessment, elective surgery, and postoperative management of CRC patients was explored by a 35-item survey, which was distributed worldwide to members of surgical societies with an interest in CRC care. Respondents were divided into two comparator groups: 1) ‘delay’ group: CRC care affected by the pandemic; 2) ‘no delay’ group: unaltered CRC practice. Results A total of 1,051 respondents from 84 countries completed the survey. No substantial differences in demographics were found between the ‘delay’ (745, 70.9%) and ‘no delay’ (306, 29.1%) groups. Suspension of multidisciplinary team meetings, staff members quarantined or relocated to COVID-19 units, units fully dedicated to COVID-19 care, personal protective equipment not readily available were factors significantly associated to delays in endoscopy, radiology, surgery, histopathology and prolonged chemoradiation therapy-to-surgery intervals. In the ‘delay’ group, 48.9% of respondents reported a change in the initial surgical plan and 26.3% reported a shift from elective to urgent operations. Recovery of CRC care was associated with the status of the outbreak. Practicing in COVID-free units, no change in operative slots and staff members not relocated to COVID-19 units were statistically associated with unaltered CRC care in the ‘no delay’ group, while the geographical distribution was not. Conclusions Global changes in diagnostic and therapeutic CRC practices were evident. Changes were associated with differences in health-care delivery systems, hospital’s preparedness, resources availability, and local COVID-19 prevalence rather than geographical factors. Strategic planning is required to optimize CRC care., Global changes in both diagnostic and therapeutic practices in colorectal cancer care were evident in this survey conducted to analyze the impact of COVID-19 outbreak. The importance of this finding is that changes were associated with differences in health care delivery systems, hospital’s preparedness, resources availability, and local COVID-19 prevalence rather than geographical variations. more...
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- 2021
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33. Impact of Hearing Rehabilitation Using Cochlear Implants on Cognitive Function in Older Patients
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C Issing, Johannes Pantel, Uwe Baumann, and Timo Stöver
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Aged, 80 and over ,medicine.medical_specialty ,Rehabilitation ,business.industry ,Hearing Tests ,medicine.medical_treatment ,Confounding ,Trail Making Test ,Cognition ,Aural rehabilitation ,Cochlear Implantation ,Sensory Systems ,Cochlear Implants ,Hearing ,Otorhinolaryngology ,Older patients ,Cochlear implant ,Physical therapy ,medicine ,Humans ,Observational study ,Neurology (clinical) ,business ,Aged - Abstract
OBJECTIVE To assess the effects of hearing rehabilitation with cochlear implants on a subset of cognitive domains in older patients (≥65 yr). STUDY DESIGN Prospective observational study. SETTING Department of Oto-Rhino-Laryngology, Goethe-University Frankfurt/Main. PATIENTS Patients aged between 65 and 86 years who have received unilateral cochlear implant (CI) therapy. INTERVENTION Unilateral cochlear implantation. MAIN OUTCOME MEASURES The dementia screening test (DemTect) and the trail making test (TMT) were carried out on three occasions: previous to the surgery, at the initial fitting (about 1 month after surgery) and 6 months after surgery. RESULTS The average overall score on the DemTect scale increased significantly within 6 months of CI treatment (p = 0.049), with verbal aspects improving particularly markedly. The results of the trail making test showed that within 6 months of CI treatment, processing speed increased significantly (TMT A: p = 0.003; TMT B: p = 0.001). CONCLUSION A pre-post comparison showed that aural rehabilitation with a CI results in an improvement in cognitive subdomains. Further comprehensive randomized-controlled studies may be necessary to evaluate possible confounding variables and to assess long-term results. more...
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- 2021
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34. Functional 4-D clustering for characterizing intratumor heterogeneity in dynamic imaging: evaluation in FDG PET as a prognostic biomarker for breast cancer
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David A. Mankoff, Eric A. Cohen, Austin R. Pantel, Aimilia Gastounioti, Mark Muzi, Varsha Viswanath, Rhea Chitalia, Joel S. Karp, Despina Kontos, and Lanell M. Peterson
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Oncology ,medicine.medical_specialty ,Dynamic imaging ,Concordance ,medicine.medical_treatment ,Breast Neoplasms ,Dynamic PET ,030218 nuclear medicine & medical imaging ,Targeted therapy ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Text mining ,Fluorodeoxyglucose F18 ,Internal medicine ,Cluster Analysis ,Humans ,Medicine ,Radiology, Nuclear Medicine and imaging ,Cluster analysis ,business.industry ,Correction ,General Medicine ,Image segmentation ,Prognosis ,medicine.disease ,Hierarchical clustering ,Positron-Emission Tomography ,030220 oncology & carcinogenesis ,Imaging markers ,Intratumor heterogeneity ,Female ,Original Article ,Neoplasm Recurrence, Local ,business ,Biomarkers - Abstract
Purpose Probe-based dynamic (4-D) imaging modalities capture breast intratumor heterogeneity both spatially and kinetically. Characterizing heterogeneity through tumor sub-populations with distinct functional behavior may elucidate tumor biology to improve targeted therapy specificity and enable precision clinical decision making. Methods We propose an unsupervised clustering algorithm for 4-D imaging that integrates Markov-Random Field (MRF) image segmentation with time-series analysis to characterize kinetic intratumor heterogeneity. We applied this to dynamic FDG PET scans by identifying distinct time-activity curve (TAC) profiles with spatial proximity constraints. We first evaluated algorithm performance using simulated dynamic data. We then applied our algorithm to a dataset of 50 women with locally advanced breast cancer imaged by dynamic FDG PET prior to treatment and followed to monitor for disease recurrence. A functional tumor heterogeneity (FTH) signature was then extracted from functionally distinct sub-regions within each tumor. Cross-validated time-to-event analysis was performed to assess the prognostic value of FTH signatures compared to established histopathological and kinetic prognostic markers. Results Adding FTH signatures to a baseline model of known predictors of disease recurrence and established FDG PET uptake and kinetic markers improved the concordance statistic (C-statistic) from 0.59 to 0.74 (p = 0.005). Unsupervised hierarchical clustering of the FTH signatures identified two significant (p p = 0.04) across the two phenotypes. Conclusions Our findings suggest that imaging markers of FTH add independent value beyond standard PET imaging metrics in predicting recurrence-free survival in breast cancer and thus merit further study. more...
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- 2021
35. Diagnostic Performance of 18F-DCFPyL-PET/CT in Men with Biochemically Recurrent Prostate Cancer: Results from the CONDOR Phase III, Multicenter Study
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Barry A. Siegel, Austin R. Pantel, Michael J. Morris, Tess Lin, Janet Pollard, Lawrence Saperstein, Steve Y. Cho, Steven P. Rowe, Kenneth L. Gage, Jessica Jensen, Frédéric Pouliot, Andrei Iagaru, David Y. Josephson, Vivien Wong, Morand Piert, Nancy Stambler, Peter R. Carroll, Jeffrey Y.C. Wong, and Michael A. Gorin more...
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Biochemical recurrence ,Cancer Research ,PET-CT ,business.industry ,Prostatectomy ,medicine.medical_treatment ,medicine.disease ,Confidence interval ,Radiation therapy ,Prostate cancer ,Oncology ,Clinical endpoint ,medicine ,Nuclear medicine ,business ,Prospective cohort study - Abstract
Purpose: Current FDA-approved imaging modalities are inadequate for localizing prostate cancer biochemical recurrence (BCR). 18F-DCFPyL is a highly selective, small-molecule prostate-specific membrane antigen–targeted PET radiotracer. CONDOR was a prospective study designed to determine the performance of 18F-DCFPyL-PET/CT in patients with BCR and uninformative standard imaging. Experimental Design: Men with rising PSA ≥0.2 ng/mL after prostatectomy or ≥2 ng/mL above nadir after radiotherapy were eligible. The primary endpoint was correct localization rate (CLR), defined as positive predictive value with an additional requirement of anatomic lesion colocalization between 18F-DCFPyL-PET/CT and a composite standard of truth (SOT). The SOT consisted of, in descending priority (i) histopathology, (ii) subsequent correlative imaging findings, or (iii) post-radiation PSA response. The trial was considered a success if the lower bound of the 95% confidence interval (CI) for CLR exceeded 20% for two of three 18F-DCFPyL-PET/CT readers. Secondary endpoints included change in intended management and safety. Results: A total of 208 men with a median baseline PSA of 0.8 ng/mL (range: 0.2–98.4 ng/mL) underwent 18F-DCFPyL-PET/CT. The CLR was 84.8%–87.0% (lower bound of 95% CI: 77.8–80.4). A total of 63.9% of evaluable patients had a change in intended management after 18F-DCFPyL-PET/CT. The disease detection rate was 59% to 66% (at least one lesion detected per patient by 18F-DCFPyL-PET/CT by central readers). Conclusions: Performance of 18F-DCFPyL-PET/CT achieved the study’s primary endpoint, demonstrating disease localization in the setting of negative standard imaging and providing clinically meaningful and actionable information. These data further support the utility of 18F-DCFPyL-PET/CT to localize disease in men with recurrent prostate cancer. See related commentary by True and Chen, p. 3512 more...
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- 2021
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36. COVID-19 im Alter – Die geriatrische Perspektive
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C Drebenstedt, A H Jacobs, M Meisel, Guido Michels, Roland Nau, Rainer Wirth, Clemens Becker, H. J. Heppner, Marija Djukic, Johannes Pantel, and Juergen M. Bauer
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Gynecology ,2019-20 coronavirus outbreak ,medicine.medical_specialty ,Health (social science) ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Geriatrics gerontology ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Issues, ethics and legal aspects ,Geriatrie ,Pandemie ,COVID-19 ,Altern ,Rehabilitation ,SARS-CoV-2 ,Medicine ,Geriatrics and Gerontology ,business ,Gerontology - Abstract
ZusammenfassungSchwerwiegend verlaufende COVID-19-Erkrankungen betreffen vorwiegend die ältere Bevölkerung. Die Mortalität der hospitalisierten COVID-19-Patienten im Alter über 80 Jahre liegt international bei bis zu 54 %. Daher ist ein Blick auf die Erkrankung aus geriatrischer Perspektive erforderlich. Diagnostik und Therapie der COVID-19-Erkrankung unterscheiden sich bei den älteren Patienten nicht grundsätzlich von der bei jüngeren Patienten. Allerdings ist bei Patienten im hohen Alter gehäuft mit einer atypischen Symptomatik zu rechnen. Der Rehabilitationsbedarf nach durchgemachter Infektion ist bei älteren COVID-19-Patienten deutlich höher als bei jüngeren Patienten. Paradoxerweise steht der Notwendigkeit vermehrter Rehabilitationsleistungen jedoch ein sinkendes Angebot geriatrischer Rehabilitationsmöglichkeiten gegenüber, da viele Abteilungen entweder geschlossen oder deren Behandlungskapazitäten reduziert wurden. Generell sollten Quarantäne- und Isolationsmaßnahmen in der älteren Bevölkerung verstärkt auf ihre Verhältnismäßigkeit überprüft werden, da die gesundheitlichen und emotionalen Auswirkungen gravierend sein können. Angesichts der ungünstigen Prognose bei hochaltrigen COVID-19-Patienten kommt der Berücksichtigung des Patientenwillens eine besondere Bedeutung zu. Daher sollten Angehörige und Ärzte sich frühzeitig, d. h. möglichst bereits vor dem Auftreten einer Infektion, bemühen, diesen zu eruieren und angemessen zu dokumentieren. Erfreulicherweise lassen die bisherigen Daten hoffen, dass die Impfung mit den in Deutschland zugelassenen mRNA-Impfstoffen gegen SARS-CoV‑2 auch im hohen Alter gut wirksam ist. more...
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- 2021
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37. Abstract GS4-08: Clinical utility of repeated circulating tumor cell (CTC) enumeration as early treatment monitoring tool in metastatic breast cancer (MBC) - a global pooled analysis with individual patient data
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Tanja Fehm, Luc Dirix, Stefan Sleijfer, Paola Gazzaniga, José A. García-Sáenz, Carlos Caldas, Rita Zamarchi, Karthik V. Giridhar, Lorenzo Gerratana, Massimo Cristofanilli, Luis Manso, Dimitrios Mavroudis, Kostandinos Sideras, Meredith M. Regan, Zefei Jiang, Michail Ignatiadis, Rafael Gisbert-Criado, William E. Barlow, François-Clément Bidard, Thomas W. P. Friedl, Klaus Pantel, Evi Lianidou, Daniele Generali, Jean-Yves Pierga, Sabine Riethdorf, Tracy C. Yab, Mark Jesus M. Magbanua, Jose Vidal-Martinez, Jeffrey B. Smerage, Brigitte Rack, Hope S. Rugo, Catherine Alix-Panabières, Lisa A. Carey, Minetta C. Liu, Volkmar Müller, William Jacot, Wolfgang Janni, Elisabetta Munzone, Justin Stebbing, Leon W.M.M. Terstappen, and Daniel F. Hayes more...
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Hazard ratio ,Cancer ,medicine.disease ,Metastatic breast cancer ,Primary tumor ,Log-rank test ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Circulating tumor cell ,Breast cancer ,030220 oncology & carcinogenesis ,Internal medicine ,Cohort ,medicine ,business - Abstract
Background: Several studies suggest clinical utility of serial circulating tumor cell (CTC) enumeration as a means of assessing response status in metastatic breast cancer (MBC). The aim of this study is to conduct a comprehensive pooled analysis comprising globally available data to further define and explore the role of CTC enumeration as a tool for early treatment monitoring in patients with MBC with a focus on the predictive power in different breast cancer subtypes and clinical settings. Methods: In a global effort, peer-reviewed published studies with data on repeated CTC assessments (CellSearch® technology; Menarini Silicon Biosystems; Bologna, Italy) in MBC patients were screened and investigators were asked to provide individual patient data for this pooled analysis. 2761 cases from 32 data sets with data on both baseline and one follow up CTC assessments were included in the analysis (median time interval between the two CTC assessments 35 days). Data were analyzed using log rank tests and Cox regressions to evaluate the association between serial CTC enumeration results and overall survival (OS) in the full patient cohort and defined subgroups. Results: 588 (21.3%) patients had no CTCs at both time points (neg/neg), 236 (8.5%) patients were CTC negative at baseline and CTC positive at follow up (neg/pos), 712 (25.8%) patients converted from CTC positive at baseline to CTC negative (pos/neg), and 1225 (44.4%) patients had at least one CTC at both time points (pos/pos). Log rank tests showed significant differences in OS between these four CTC change groups (p < 0.0001 for all pairwise comparisons except for the comparison between neg/pos and pos/neg, p = 0.015). Median OS for the neg/neg, neg/pos, pos/neg and pos/pos group was 45.6, 26.1, 34.6, and 17.6 months, respectively. Hazard ratios (HR) (reference group neg/neg) were 1.38 (95% CI 1.16 - 1.64) for the pos/neg group, 1.78 (95% CI 1.43 - 2.22) for the neg/pos group, and 3.06 (95% CI 2.63 - 3.56) for the pos/pos group. Results were similar if a cutoff of 5 CTCs was used for CTC positivity (pos/neg group: HR 1.43, 95% CI 1.25 - 1.63; neg/pos group: HR 2.39, 95% CI 1.91 - 2.99; pos/pos group: HR 3.54, 95% CI 3.12 - 4.02). In total, 2586 patients could be assigned to different tumor subtypes based on known hormone receptor (ER) and HER2 status of the primary tumor: 1513 (58.5%) patients had a luminal-like tumor (ER positive, HER2 negative), 682 (26.4%) patients had a HER2-positive tumor, and 391 (15.1%) patients had a triple-negative tumor. In patients with luminal-like tumors, the hazard ratios were 1.67 (95% CI 1.29 - 2.17), 2.01 (95% CI 1.45 - 2.77), and 3.87 (95% CI 3.09 - 4.83) for the pos/neg, neg/pos, and pos/pos group, respectively. In patients with HER2-positive tumors, the neg/pos group (HR 1.68, 95% CI 1.12 - 2.53) and the pos/pos group (HR 2.11, 95% CI 1.58 - 2.83) showed significantly worse OS compared to the neg/neg group, while in triple-negative patients, the pos/pos group had a significantly shorter OS compared to the neg/neg group (HR 2.99, 95% CI 2.11 - 4.24). The results will be up-dated by inclusion of additional large data sets (CALGB 40502, CALGB 40503, COMET, SWOG S0500, TBCRC 001) for the analysis to be presented at SABCS 2020. Conclusion: This large pooled analysis confirms that at a median of 35 days after treatment initiation, follow-up CTC assessments strongly predict overall survival. These results suggest potential clinical utility of CTC monitoring as early response marker in MBC, especially in luminal-like tumors. Citation Format: Wolfgang J Janni, Tracy C. Yab, Daniel F. Hayes, Massimo Cristofanilli, Francois-Clement Bidard, Michail Ignatiadis, Meredith M. Regan, Catherine Alix-Panabières, William E. Barlow, Carlos Caldas, Lisa A. Carey, Luc Dirix, Tanja Fehm, Jose A. Garcia-Saenz, Paola Gazzaniga, Daniele Generali, Lorenzo Gerratana, Rafael Gisbert-Criado, William Jacot, Zefei Jiang, Evi Lianidou, Mark J.M. Magbanua, Luis Manso, Dimitrios Mavroudis, Volkmar Müller, Elisabetta Munzone, Klaus Pantel, Jean-Yves Pierga, Brigitte Rack, Sabine Riethdorf, Hope S. Rugo, Kostandinos Sideras, Stefan Sleijfer, Jeffrey Smerage, Justin Stebbing, Leon W.M.M. Terstappen, José Vidal-Martínez, Rita Zamarchi, Karthik Giridhar, Thomas W.P. Friedl, Minetta C. Liu. Clinical utility of repeated circulating tumor cell (CTC) enumeration as early treatment monitoring tool in metastatic breast cancer (MBC) - a global pooled analysis with individual patient data [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr GS4-08. more...
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- 2021
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38. The GhsrQ343X allele favors the storage of fat by acting on nutrient partitioning
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Rim Hassouna, Raphaël G. P. Denis, Florence Noble, Serge Luquet, Daniela Cota, Gwenaëlle Le Pen, Hélène Doat, Yacine Chebani, Jacques Pantel, Thierry Leste-Lasserre, Philippe Zizzari, Candice Marion, Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire (T3S - UMR_S 1124), Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bordeaux (UB), INSERM, Neurocentre Magendie, U1215, Physiopathologie de la Plasticité Neuronale, F-33000 Bordeaux, France, Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB), Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), and Pantel, Jacques more...
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Agonist ,medicine.medical_specialty ,medicine.drug_class ,[SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] ,Endocrinology, Diabetes and Metabolism ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,Growth hormone secretagogue receptor ,030209 endocrinology & metabolism ,Energy homeostasis ,Mutant rat ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Food intake ,Internal medicine ,medicine ,[SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] ,Receptor ,030304 developmental biology ,0303 health sciences ,Chemistry ,digestive, oral, and skin physiology ,[SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,Energy metabolism ,Ghrelin ,Hypothalamus ,Dopamine receptor ,GHSR ,Hormone - Abstract
The growth hormone secretagogue receptor (GHSR) mediates key properties of the gut hormone ghrelin on metabolism and behavior. Nevertheless, most recent observations also support that the GHSR is a constitutively active G protein-coupled receptor (GPCR) endowed with a sophisticated tuning involving a balance of endogenous ligands. Demonstrating the feasibility of shifting GHSR canonical signaling in vivo, we previously reported that a model with enhanced sensitivity to ghrelin (GhsrQ343X mutant rats) developed fat accumulation and glucose intolerance. Herein, we investigated the contribution of energy homeostasis to the onset of this phenotype, as well as behavioral responses to feeding or pharmacological challenges, by comparing GhsrM/M rats to WT littermate rats: (1) as freely behaving animals and (2) in feeding and locomotor paradigms. Herein, GhsrM/M rats showed enhanced locomotor response to a GHSR agonist while locomotor or anorexigenic responses to amphetamine or cabergoline (dopamine receptor 2 agonist), respectively, were preserved. Ad libitum fedGhsrM/M rats consumed and conditioned for sucrose similarly to littermate control rats . In calorie-restricted conditions, GhsrM/M rats retained food anticipatory activity and maintained better body weight and glycemia. Importantly, prior to fat accumulation, male GhsrM/M rats preferentially used carbohydrates as fuel substrate without alterations of energy intake, energy expenditure or physical activity and showed alterations of the GHSR system (i.e. enhanced ratio of GHSR hormones LEAP2: acyl-ghrelin and increased Ghsr expression in the hypothalamus). Overall, the present study provides proof for the concept that shifted GHSR signaling can specifically alter nutrient partitioning resulting in modified balance of carbohydrate/lipid utilization. more...
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- 2021
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39. A phase I study of pazopanib in combination with escalating doses of 131I in patients with well-differentiated thyroid carcinoma borderline refractory to radioiodine.
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Laura Q Chow, Rafael Santana-Davila, Austin Pantel, Mara Roth, Leslie N Anderson, Alan Failor, Robert Doot, and David Mankoff
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Medicine ,Science - Abstract
This trial was conducted to evaluate the ability of pazopanib to overcome therapeutic 131I resistance.This phase 1 trial assesses the combination of pazopanib and escalating doses of radioiodine (131I) in patients with recurrent or metastatic thyroid cancer that are borderline or relatively iodine refractory. Radioiodine uptake scans were assessed post therapy and compared to historical pre-treatment scans. Patients underwent FDG PET/CT before and after the initial pazopanib treatment to identify the impact of pazopanib on the cancer prior to 131I therapy.A dose limiting toxicity (cardiac arrhythmia and grade 3 fatigue) in the first patient in the first cohort prompted expansion to a total of 6 patients. Additional grade 3-4 hematologic toxicity and low accrual in the expanded cohort led to the decision not to pursue further study of the regimen. In patients with measurable disease 4/5 (80%) achieved stable disease. Median progression free survival was 6.7 months. At 3 years of follow up, one patient died due to progressive disease, two are being treated with systemic therapy and 3 continue without requiring subsequent therapy at 15, 27 and 35 months from the last dose of pazopanib. There was no convincing impact of pazopanib on iodine uptake in scans performed pre- and post-therapy compared to scans from historical 131I treatments without pazopanib.Despite a suggestion of therapeutic efficacy, combined pazopanib and 131I resulted in increased toxicity. There was no convincing evidence that the administration of pazopanib improved iodine uptake or retention.ClinicalTrials.gov NCT01413113. more...
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- 2017
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40. A segmentation-based volumetric approach to localize and quantify cerebral vasospasm based on tomographic imaging data.
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Axel Neulen, Tobias Pantel, Michael Kosterhon, Stefanie Kirschner, Marc A Brockmann, Sven R Kantelhardt, Alf Giese, and Serge C Thal
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Medicine ,Science - Abstract
Quantification of cerebral vasospasm after subarachnoid hemorrhage (SAH) is crucial in animal studies as well as clinical routine. We have developed a method for computer-based volumetric assessment of intracranial blood vessels from cross-sectional imaging data. Here we demonstrate the quantification of vasospasm from micro computed tomography (micro-CT) data in a rodent SAH model and the transferability of the volumetric approach to clinical data.We obtained rodent data by performing an ex vivo micro-CT of murine brains after sham surgery or SAH by endovascular filament perforation on day 3 post hemorrhage. Clinical CT angiography (CTA) was performed for diagnostic reasons unrelated to this study. We digitally reconstructed and segmented intracranial vascular trees, followed by calculating volumes of defined vessel segments by standardized protocols using Amira® software.SAH animals demonstrated significantly smaller vessel diameters compared with sham (MCA: 134.4±26.9μm vs.165.0±18.7μm, p more...
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- 2017
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41. Integrin alpha5 in human breast cancer is a mediator of bone metastasis and a therapeutic target for the treatment of osteolytic lesions
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Keltouma Driouch, Sandra Geraci, Michele Iuliani, Philippe Clézardin, Martine Croset, Bruno Vincenzi, Klaus Pantel, Francesco Pantano, Giulia Ribelli, Natalia Bednarz-Knoll, Edith Bonnelye, Daniele Santini, Giuseppe Tonini, Harriet Wikman, Florian Bonin, Sofia Sousa, Saw See Hong, Sonia Simonetti, Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases (LYOS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Biologie tumorale [Institut Curie, Paris], Institut Curie [Paris], Service de génétique, Institut Curie Paris, Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Infections Virales et Pathologie Comparée - UMR 754 (IVPC), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), BONNELYE, Edith, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA) more...
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0301 basic medicine ,Integrins ,Cancer Research ,Volociximab ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Bone Neoplasms ,Breast Neoplasms ,Kaplan-Meier Estimate ,Osteolysis ,Biology ,medicine.disease_cause ,Article ,Bone resorption ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,Cell Movement ,Cell Line, Tumor ,Cell Adhesion ,Genetics ,medicine ,Humans ,Neoplasm Metastasis ,Molecular Biology ,Aged ,Cell Proliferation ,Bone metastases ,Antibodies, Monoclonal ,Cancer ,Bone metastasis ,Middle Aged ,medicine.disease ,Progression-Free Survival ,3. Good health ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Cancer research ,Female ,Bone marrow ,Neoplasm Recurrence, Local ,Carcinogenesis ,medicine.drug - Abstract
Bone metastasis remains a major cause of mortality and morbidity in breast cancer. Therefore, there is an urgent need to better select high-risk patients in order to adapt patient’s treatment and prevent bone recurrence. Here, we found that integrin alpha5 (ITGA5) was highly expressed in bone metastases, compared to lung, liver, or brain metastases. High ITGA5 expression in primary tumors correlated with the presence of disseminated tumor cells in bone marrow aspirates from early stage breast cancer patients (n = 268; p = 0.039). ITGA5 was also predictive of poor bone metastasis-free survival in two separate clinical data sets (n = 855, HR = 1.36, p = 0.018 and n = 427, HR = 1.62, p = 0.024). This prognostic value remained significant in multivariate analysis (p = 0.028). Experimentally, ITGA5 silencing impaired tumor cell adhesion to fibronectin, migration, and survival. ITGA5 silencing also reduced tumor cell colonization of the bone marrow and formation of osteolytic lesions in vivo. Conversely, ITGA5 overexpression promoted bone metastasis. Pharmacological inhibition of ITGA5 with humanized monoclonal antibody M200 (volociximab) recapitulated inhibitory effects of ITGA5 silencing on tumor cell functions in vitro and tumor cell colonization of the bone marrow in vivo. M200 also markedly reduced tumor outgrowth in experimental models of bone metastasis or tumorigenesis, and blunted cancer-associated bone destruction. ITGA5 was not only expressed by tumor cells but also osteoclasts. In this respect, M200 decreased human osteoclast-mediated bone resorption in vitro. Overall, this study identifies ITGA5 as a mediator of breast-to-bone metastasis and raises the possibility that volociximab/M200 could be repurposed for the treatment of ITGA5-positive breast cancer patients with bone metastases. more...
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- 2021
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42. Enumeration and Changes in Circulating Tumor Cells and Their Prognostic Value in Patients Undergoing Cytoreductive Radical Prostatectomy for Oligometastatic Prostate Cancer—Translational Research Results from the Prospective ProMPT trial
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Hartwig Huland, Philipp Mandel, Derya Tilki, Lars Budäus, Felix K.-H. Chun, Alexander Haese, Markus Graefen, Klaus Pantel, Georg Salomon, Hans Heinzer, Sabine Riethdorf, Anne Tiebel, and Thomas Steuber more...
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Male ,Oncology ,medicine.medical_specialty ,Urology ,medicine.medical_treatment ,030232 urology & nephrology ,Translational research ,Translational Research, Biomedical ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Circulating tumor cell ,Robotic Surgical Procedures ,Prostate ,Internal medicine ,Prevalence ,medicine ,Humans ,In patient ,Prospective Studies ,Patient summary ,Prostatectomy ,business.industry ,Prostatic Neoplasms ,Small sample ,Cytoreduction Surgical Procedures ,Neoplastic Cells, Circulating ,Prognosis ,medicine.disease ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,business ,Biomarkers - Abstract
Background The prognostic value of circulating tumor cells (CTCs) in patients with hormone-naive oligometastatic prostate cancer (HNoMPC) undergoing cytoreductive radical prostatectomy (CRP) is unknown. Objective To determine the pre- and postoperative prognostic value of CTC enumeration in patients undergoing CRP. Design, setting, and participants Thirty-three patients with HNoMPC from the prospective, single-arm ProMPT trial who underwent CRP between 2014 and 2015 at the Martini-Klinik were evaluated. Follow-up visits for all patients were conducted every 6 mo up to 36 mo after CRP and included serial detection of CTCs in 7.5 ml blood samples using the CellSearch system. Intervention CRP. Outcome measurements and statistical analysis CTC enumerations before and after CRP, and their prognostic value on metastatic castration-resistant prostate cancer–free survival and overall survival (OS) were analyzed using Kaplan-Meier plots and univariable Cox-regression analysis. Results and limitations Sixteen patients (48.5%) had positive CTCs prior to CRP. A CTC count of ≥2 before or 6 mo after CRP was a prognostic factor for worse oncologic outcome. Compared with other biomarkers (prostate-specific antigen, lactate dehydrogenase, and bone-specific alkaline phosphatase), the prognostic value of CTCs was highest using Harrell’s C for OS (0.69), while the highest C-index could be achieved for a combination of conventional markers and CTC count (0.74). After progression to metastatic castration-resistant prostate cancer, CTC enumeration of ≥5 was prognostic for OS. The main limitation is the small sample size. Conclusions CTC enumeration contributes to prognostic information, which might help select HNoMPC patients who might benefit most from CRP. Patient summary In this report, we looked at the value of circulating tumor cell (CTC) determination in patients undergoing radical prostatectomy for oligometastatic prostate cancer. We could show that the number of CTCs was a prognostic factor at all analyzed time points and was more closely associated with prognosis than other biomarkers commonly used in daily clinical practice. more...
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- 2021
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43. Analysis of Four-Dimensional Data for Total Body PET Imaging
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Austin R. Pantel, Rhea Chitalia, Joel S. Karp, David A. Mankoff, and Varsha Viswanath
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Radiation ,business.industry ,Dynamic imaging ,Total body ,General Medicine ,Pet imaging ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Pet scanner ,Parametric imaging ,Medicine ,Radiology, Nuclear Medicine and imaging ,Sensitivity (control systems) ,business ,Biomedical engineering - Abstract
The high sensitivity and total-body coverage of total-body PET scanners will be valuable for a number of clinical and research applications outlined in this article.
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- 2021
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44. Update on the PennPET Explorer
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Joel S. Karp, Austin R. Pantel, and Varsha Viswanath
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Scanner ,Radiation ,medicine.diagnostic_test ,business.industry ,General Medicine ,Axial field ,Positron emission tomography ,Scalability ,Medicine ,Radiology, Nuclear Medicine and imaging ,Instrumentation (computer programming) ,business ,Whole body ,Computer hardware - Abstract
Following successful performance testing and human imaging of a prototype PennPET Explorer, the scanner has been expanded to a current axial field of view of 1.12 m. Initial studies on this instrument have demonstrated encouraging results for total-body positron emission tomography imaging. Planned studies will test the capabilities of the PennPET Explorer further and inform the design of further human imaging protocols. more...
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- 2021
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45. Oncologic Applications of Long Axial Field-of-View PET/Computed Tomography
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Lorenzo Nardo and Austin R. Pantel
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Image quality ,ComputingMethodologies_IMAGEPROCESSINGANDCOMPUTERVISION ,Bioengineering ,Computed tomography ,Medical Oncology ,Article ,030218 nuclear medicine & medical imaging ,Axial field ,03 medical and health sciences ,0302 clinical medicine ,Neoplasms ,Positron Emission Tomography Computed Tomography ,EXPLORER ,Humans ,Medicine ,Dosimetry ,Whole Body Imaging ,Radiology, Nuclear Medicine and imaging ,Human imaging ,Cancer ,screening and diagnosis ,Radiation ,medicine.diagnostic_test ,business.industry ,Reproducibility of Results ,General Medicine ,Whole-body imager ,Detection ,Nuclear Medicine & Medical Imaging ,PET ,Oncology ,Early results ,030220 oncology & carcinogenesis ,Pet scanner ,Biomedical Imaging ,Cell tracking ,business ,4.2 Evaluation of markers and technologies ,Biomedical engineering - Abstract
New protocols for imaging cancer have been developed to take advantage of the improved imaging capabilities of long axial field-of-view PET scanners. Both research and clinical applications have been pursued with encouraging early results. Clinical studies have demonstrated improved image quality and the ability to image with less injected activity or for shorter duration. With the increased sensitivity inherent in total-body PET scanners and new imaging paradigms, new challenges in image interpretation have emerged. New research applications have also emerged, including dosimetry, cell tracking, and dual-tracer applications. more...
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- 2021
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46. Sensitive Blood-Based Detection of Asbestos-Associated Diseases Using Cysteine-Rich Angiogenic Inducer 61 as Circulating Protein Biomarker
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Sven Peine, Thomas Brüning, Daniel G. Weber, Simon A. Joosse, Klaus Pantel, Swaantje Casjens, Lucija Ačkar, Antje Andreas, Maria Geffken, Irina Raiko, Georg Johnen, and Kai Bartkowiak
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Male ,Mesothelioma ,0301 basic medicine ,medicine.medical_specialty ,Clinical Biochemistry ,Asbestosis ,Youden's J statistic ,Enzyme-Linked Immunosorbent Assay ,Disease ,Sensitivity and Specificity ,Peripheral blood mononuclear cell ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Humans ,Medicine ,Aged ,Aged, 80 and over ,business.industry ,Biochemistry (medical) ,Area under the curve ,Middle Aged ,medicine.disease ,030104 developmental biology ,Case-Control Studies ,030220 oncology & carcinogenesis ,Biomarker (medicine) ,Female ,business ,Biomarkers ,Cysteine-Rich Protein 61 ,Cohort study - Abstract
Background Detection of asbestos-associated diseases like asbestosis or mesothelioma is still challenging. We sought to improve the diagnosis of benign asbestos-associated disease (BAAD) by detection of the protein cysteine-rich angiogenic inducer 61 (Cyr61) in human plasma. Methods Plasma Cyr61 was quantified using an enzyme-linked immunosorbent assay. Plasma samples from males diagnosed with BAAD, but without a malignant disease (n = 101), and malignant mesothelioma (n = 21; 15 males, 6 females), as well as nonasbestos-exposed healthy control participants (n = 150; 58 males, 92 females) were analyzed. Clinical sensitivity and specificity of Cyr61 were determined by receiver operating characteristic analysis. Results The median plasma Cyr61 concentration for healthy control participants was 0.27 ng/mL. Cytoplasmic Cyr61 in peripheral blood mononuclear cells from healthy control participants was evenly distributed, as detected by immunofluorescent staining. The increase in plasma Cyr61 concentrations in the BAAD study group was statistically significant compared to the healthy control participants (P Conclusions In our study, plasma Cyr61 protein concentrations showed to be a new biomarker for asbestos-associated diseases like BAAD and mesothelioma in men, which deserves further investigation in large-scale cohort studies. more...
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- 2020
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47. Copy number variations in primary tumor, serum and lymph node metastasis of bladder cancer patients treated with radical cystectomy
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Roland Dahlem, Tim A. Ludwig, Christian Meyer, Bettina Steinbach, Guido Sauter, Klaus Pantel, Hang Yu, Heidi Schwarzenbach, Philipp Gild, Armin Soave, Margit Fisch, Lan Kluwe, Michael Rink, Malte W. Vetterlein, Sarah Minner, and Philipp Marks more...
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0301 basic medicine ,Male ,DNA Copy Number Variations ,Receptor, ErbB-2 ,Molecular biology ,medicine.medical_treatment ,Urology ,Science ,Cystectomy ,Article ,Proto-Oncogene Proteins c-myc ,03 medical and health sciences ,0302 clinical medicine ,Cyclin D1 ,Cyclin E ,medicine ,Humans ,Copy-number variation ,Multiplex ligation-dependent probe amplification ,Gene ,Aged ,Cancer ,Aged, 80 and over ,Oncogene Proteins ,Multidisciplinary ,Bladder cancer ,business.industry ,Middle Aged ,medicine.disease ,Primary tumor ,eye diseases ,genomic DNA ,030104 developmental biology ,Urinary Bladder Neoplasms ,030220 oncology & carcinogenesis ,Lymphatic Metastasis ,Cancer research ,Lymph Node Excision ,Medicine ,Female ,business ,Multiplex Polymerase Chain Reaction - Abstract
The aim of the present study was to analyze copy number variations (CNV) of multiple oncogenes and tumor suppressor genes in genomic DNA from primary tumor tissue, lymph node metastasis and cell-free DNA (cfDNA) from serum of 72 urothelial carcinoma of bladder (UCB) patients treated with radical cystectomy (RC), using multiplex ligation-dependent probe amplification (MLPA). We hypothesized that primary tumor and lymph node metastasis show similar CNV profiles, and CNV are more present in lymph node metastasis compared to primary tumor tissue. Samples from 43 (59.7%) patients could be analyzed. In total, 35 (83%), 26 (68%) and 8 (42%) patients had CNV in primary tumor, serum and lymph node metastasis, respectively. MYC, CCND1, ERBB2 and CCNE1 displayed the most frequent amplifications. In particular, CNV in ERBB2 was associated with aggressive tumor characteristics. CNV in both ERBB2 and TOP2A were risk factors for disease recurrence. The current findings show that CNV are present in various oncogenes and tumor suppressor genes in genomic DNA from primary tumor, lymph node metastasis and cfDNA from serum. CNV were more present in genomic DNA from primary tumor tissue compared to cfDNA from serum and genomic DNA from lymph node metastasis. Patients with CNV in ERBB2 and TOP2A are at increased risk for disease recurrence following RC. Further studies are necessary to validate, whether these genes may represent promising candidates for targeted-therapy. more...
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- 2020
48. Kindliche Hörstörungen – Einteilung, Diagnostik und Therapie
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A Nolte, Ruth Lang-Roth, Martin Otte, and Gitta Pantel
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business.industry ,Medicine ,business - Published
- 2020
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49. Update on Quantitative Imaging for Predicting and Assessing Response in Oncology
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David A. Mankoff, Christine E Edmonds, Jennifer Gillman, and Austin R. Pantel
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Oncology ,medicine.medical_specialty ,business.industry ,MEDLINE ,Context (language use) ,Disease ,Precision medicine ,medicine.disease ,Article ,Molecular Imaging ,Treatment Outcome ,Breast cancer ,Neoplasms ,Internal medicine ,medicine ,Humans ,Biomarker (medicine) ,Radiology, Nuclear Medicine and imaging ,Molecular imaging ,business ,Lung cancer - Abstract
Molecular imaging has revolutionized clinical oncology by imaging specific facets of cancer biology. Through non-invasive measurements of tumor physiology, targeted radiotracers can serve as biomarkers for disease characterization, prognosis, response assessment, and predicting long-term response / survival. In turn, these imaging biomarkers can be utilized to tailor therapeutic regimens to tumor biology. In this article, we review biomarker applications for response assessment and predicting long-term outcomes. F-fluorodeoxyglucose (FDG), a measure of cellular glucose metabolism, is discussed in the context of lymphoma and breast and lung cancer. FDG has gained widespread clinical acceptance and has been integrated into the routine clinical care of several malignancies, most notably lymphoma. The novel radiotracers 16α−(18)F-fluoro-17β-estradiol (FES), and (18)F-fluorothymidine (FLT) are reviewed in application to the early prediction of response assessment of breast cancer. Through illustrative examples, we explore current and future applications of molecular imaging biomarkers in the advancement of precision medicine. more...
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- 2020
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50. Quantifying Bias and Precision of Kinetic Parameter Estimation on the PennPET Explorer, a Long Axial Field-of-View Scanner
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Mark Muzi, Margaret E. Daube-Witherspoon, Robert K. Doot, Joel S. Karp, Varsha Viswanath, Austin R. Pantel, and David A. Mankoff
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Physics ,Scanner ,medicine.diagnostic_test ,Estimation theory ,Dynamic imaging ,Flux ,Kinetic energy ,Article ,Atomic and Molecular Physics, and Optics ,Imaging phantom ,Computational physics ,Positron emission tomography ,medicine ,Radiology, Nuclear Medicine and imaging ,Sensitivity (control systems) ,Instrumentation - Abstract
Long axial field-of-view (AFOV) PET scanners allow for full-body dynamic imaging in a single bed-position at very high sensitivity. However, the benefits for kinetic parameter estimation have yet to be studied. This work uses 1) a dynamic Geant4 Application for Tomographic Emission (GATE) simulation of [18F]-fluorothymidine (FLT) in a modified NEMA IQ phantom and 2) a lesion embedding study of spheres in a dynamic [18F]-fluorodeoxyglucose (FDG) human subject imaged on the PennPET Explorer. Both studies were designed using published kinetic data of lung and liver cancers and modeled using two tissue compartments. Data were reconstructed at various emulated doses. Sphere time-activity curves (TACs) were measured on resulting dynamic images, and TACs were fit using a two-tissue-compartment model ( $k_{4}\neq 0$ ) for the FLT study and both a two-tissue-compartment model ( $k_{4}=0$ ) and Patlak graphical analysis for the FDG study to estimate flux ( $K_{i}$ ) and delivery ( $K_{1}$ ) parameters. Quantification of flux and $K_{1}$ shows lower bias and better precision for both radiotracers on the long AFOV scanner, especially at low doses. Dynamic imaging on a long AFOV system can be achieved for a greater range of injected doses, as low as 0.5–2 mCi depending on the sphere size and flux, compared to a standard AFOV scanner, while maintaining good kinetic parameter estimation. more...
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- 2020
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