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141.
Esther G C Troost Johan Bussink Johannes H A M Kaanders Julli?tte van Eerd Johannes P W Peters Paulus F J W Rijken Otto C Boerman Albert J van der Kogel 《Radiotherapy and oncology》2005,76(2):194-199
PURPOSE: In head and neck cancer, it has been shown that hypoxic tumors respond poorly to therapy. Methods to identify hypoxic tumors are, therefore, of importance to select patients for oxygenation modifying or other intensified treatments. The aim of this study was to compare tumor cell hypoxia assessed by the hypoxic cell marker pimonidazole (PIMO) with expression of the endogenous hypoxia-related marker carbonic anhydrase IX (CAIX) in three human head and neck tumor lines. MATERIAL AND METHODS: Forty-five tumors of three human head and neck tumor lines, SCCNij3, SCCNij59 and MEC82, xenografted in athymic mice, were used. CAIX was quantified by biodistribution (% injected dose/g tumor) after injecting 3-5 microl 111In-labeled G250 mouse antibody 3 days prior to euthanizing. In a tissue section from the same tumor, fractions of tumor area positive for PIMO, CAIX and Hoechst 33342 (perfusion marker) were assessed after immunohistochemical staining, using a digital image analysis system. RESULTS: SCCNij3 and MEC82 were relatively hypoxic tumor lines with fractions of tumor area positive for pimonidazole of 0.16 and 0.15, respectively. SCCNij59 was a better-oxygenated tumor line with a PIMO-fraction of 0.03. The three tumor lines showed different levels and patterns of CAIX immunohistochemical staining, but only in MEC82 there was a good correlation between PIMO-fraction and CAIX-fraction (r2=0.92, P<0.0001). Correlations between 111In-G250 uptake and CAIX-fraction or PIMO-fraction within tumor lines were weak or absent. CONCLUSIONS: Assessment of CAIX expression depends largely on the techniques and tumor lines used. Furthermore, the immunohistochemical staining pattern of CAIX relative to PIMO differs between human tumor lines of similar anatomical origin. Therefore, the use of CAIX as endogenous marker of tumor hypoxia remains questionable. 相似文献
142.
Phase II study of oxaliplatin for treatment of patients with mucosa-associated lymphoid tissue lymphoma. 总被引:4,自引:0,他引:4
Markus Raderer Stefan W?hrer Rupert Bartsch Gerald Prager Johannes Drach Michael Hejna Alexander Gaiger Karl Turetschek Ulrich Jaeger Berthold Streubel Christoph C Zielinski 《Journal of clinical oncology》2005,23(33):8442-8446
PURPOSE: Various chemotherapeutic regimens have been applied for treatment of mucosa-associated lymphoid tissue (MALT) lymphoma, but no standard regimen has been identified to date. In view of the activity of oxaliplatin (L-OHP) in various types of lymphoma, we performed a phase II study to evaluate the activity of L-OHP for treatment of MALT lymphoma. The primary objective of this study was to determine the objective response rate according to WHO standard criteria. PATIENTS AND METHODS: A total of 16 patients with MALT lymphoma of various sites of origin (four of the ocular adnexa, five of the salivary glands, three of the stomach, two of the lung, and one of the colon and the breast) were administered L-OHP at a dose of 130 mg/m2 infused during 2 hours every 3 weeks. Restaging was performed every two cycles; treatment was continued until complete remission (CR) or for a maximum of six cycles in responders. RESULTS: Sixty-five cycles were administered (median, four; range, two to six); toxicity consisted of transient sensory neuropathy in eight patients and nausea/emesis WHO grade 2 in two patients, whereas hematologic adverse effects (thrombocytopenia and leukocytopenia grade 2) occurred in only one patient each. Fifteen patients responded to chemotherapy, with nine achieving CR (56%), six (37.5%) achieving partial response, and one achieving stable disease; the median time to response was 4 months (range; 2 to 4 months). CONCLUSION: These data suggest L-OHP is a highly active agent for treatment of MALT lymphoma. However, a longer follow-up is needed to judge whether these remissions are durable. 相似文献
143.
Cerebrospinal anandamide levels are elevated in acute schizophrenia and are inversely correlated with psychotic symptoms. 总被引:7,自引:0,他引:7
Andrea Giuffrida F Markus Leweke Christoph W Gerth Daniela Schreiber Dagmar Koethe Johannes Faulhaber Joachim Klosterk?tter Daniele Piomelli 《Neuropsychopharmacology》2004,29(11):2108-2114
The endocannabinoids are a family of bioactive lipids that activate CB1 cannabinoid receptors in the brain and exert intense emotional and cognitive effects. Here, we have examined the role of endocannabinoid signaling in psychotic states by measuring levels of the endocannabinoid anandamide in cerebrospinal fluid (CSF) of acute paranoid-type schizophrenic patients. We found that CSF anandamide levels are eight-fold higher in antipsychotic-naive first-episode paranoid schizophrenics (n = 47) than healthy controls (n = 84), dementia patients (n = 13) or affective disorder patients (n = 22). Such an alteration is absent in schizophrenics treated with 'typical' antipsychotics (n = 37), which antagonize dopamine D2-like receptors, but not in those treated with 'atypical' antipsychotics (n = 34), which preferentially antagonize 5HT(2A) receptors. Furthermore, we found that, in nonmedicated acute schizophrenics, CSF anandamide is negatively correlated with psychotic symptoms (rS = -0.452, P = 0.001). The results suggest that anandamide elevation in acute paranoid schizophrenia may reflect a compensatory adaptation to the disease state. 相似文献
144.
Floor A.M. Postema Jet Bliek Carel J.M. van Noesel Laura J.C.M. van Zutven Jan C. Oosterwijk Saskia M. J. Hopman Johannes H. M. Merks Raoul C. Hennekam 《Pediatric blood & cancer》2019,66(6)
Mosaic genome‐wide paternal uniparental disomy is an infrequently described disorder in which affected individuals have signs and symptoms that may resemble Beckwith–Wiedemann syndrome. In addition, they can develop multiple benign and malignant tumors throughout life. Routine molecular diagnostics may not detect the (characteristic) low level of mosaicism, and the diagnosis is likely to be missed. Genetic counseling and a life‐long alertness for the development of tumors is indicated. We describe the long diagnostic process of a patient who already had a tumor at birth and developed multiple tumors in childhood and adulthood. Furthermore, we offer clues to recognize the entity. 相似文献
145.
Katinka Breuer Korbinian M. Riedhammer Nicole Müller Birthe Schaidinger Gregor Dombrowsky Sven Dittrich Susanne Zeidler Ulrike M. M. Bauer Dominik S. Westphal Thomas Meitinger Tikam Chand Dakal Marc-Phillip Hitz Johannes Breuer Heiko Reutter Alina C. Hilger Julia Hoefele 《European journal of human genetics : EJHG》2022,30(8):946
The birth prevalence of laterality defects is about 1.1/10,000 comprising different phenotypes ranging from situs inversus totalis to heterotaxy, mostly associated with complex congenital heart defects (CHD) and situs abnormalities such as intestinal malrotation, biliary atresia, asplenia, or polysplenia. A proportion of laterality defects arise in the context of primary ciliary dyskinesia (PCD) accompanied by respiratory symptoms or infertility. In this study, exome sequencing (ES) was performed in 14 case-parent trios/quattros with clinical exclusion of PCD prior to analysis. Moreover, all cases and parents underwent detailed clinical phenotyping including physical examination, echocardiography by a skilled paediatric cardiologist and abdominal ultrasound examinations not to miss mildly affected individuals. Subsequent survey of the exome data comprised filtering for monoallelic de novo, rare biallelic, and X-linked recessive variants. In two families, rare variants of uncertain significance (VUS) in PKD1L1 and ZIC3 were identified. Both genes have been associated with laterality defects. In two of the remaining families, biallelic variants in LMBRD1 and DNAH17, respectively, were prioritized. In another family, an ultra-rare de novo variant in WDR47 was found. Extensive exome survey of 2,109 single exomes of individuals with situs inversus totalis, heterotaxy, or isolated CHD identified two individuals with novel monoallelic variants in WDR47, but no further individuals with biallelic variants in DNAH17 or LMBRD1. Overall, ES of 14 case-parent trios/quattros with cardiovascular laterality defects identified rare VUS in two families in known disease-associated genes PKD1L1 and ZIC3 and suggests DNAH17, LMBRD1, and WDR47 as potential genes involved in laterality defects.Subject terms: Disease genetics, Genetic counselling, Biological sciences 相似文献
146.
Ilona Krey Sarah von Spiczak Kathrine M. Johannesen Christiane Hikel Gerhard Kurlemann Hiltrud Muhle Diane Beysen Tobias Dietel Rikke S. Mller Johannes R. Lemke Steffen Syrbe 《Neurotherapeutics》2022,19(1):334
Pathogenic missense variants in GRIN2A and GRIN2B may result in gain or loss of function (GoF/LoF) of the N-methyl-D-aspartate receptor (NMDAR). This observation gave rise to the hypothesis of successfully treating GRIN-related disorders due to LoF variants with co-agonists of the NMDAR. In this respect, we describe a retrospectively collected series of ten individuals with GRIN2A- or GRIN2B-related disorders who were treated with L-serine, each within an independent n-of-1 trial. Our cohort comprises one individual with a LoF missense variant with clinical improvements confirming the above hypothesis and replicating a previous n-of-1 trial. A second individual with a GoF missense variant was erroneously treated with L-serine and experienced immediate temporary behavioral deterioration further supporting the supposed functional pathomechanism. Eight additional individuals with null variants (that had been interpreted as loss-of-function variants despite not being missense) again showed clinical improvements. Among all nine individuals with LoF missense or null variants, L-serine treatment was associated with improvements in behavior in eight (89%), in development in four (44%), and/or in EEG or seizure frequency in four (44%). None of these nine individuals experienced side effects or adverse findings in the context of L-serine treatment. In summary, we describe the first evidence that L-serine treatment may not only be associated with clinical improvements in GRIN-related disorders due to LoF missense but particularly also null variants.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13311-021-01173-9. 相似文献
147.
Rita K. Schmutzler Bjrn Schmitz-Luhn Bettina Borisch Peter Devilee Diana Eccles Per Hall Judith Balmaa Stefania Boccia Peter Dabrock Günter Emons Wolfgang Gaissmaier Jacek Gronwald Stefanie Houwaart Stefan Huster Karin Kast Alexander Katalinic Sabine C. Linn Sowmiya Moorthie Paul Pharoah Kerstin Rhiem Tade Spranger Dominique Stoppa-Lyonnet Johannes Jozef Marten van Delden Marc van den Bulcke Christiane Woopen 《Breast care (Basel, Switzerland)》2022,17(2):208
BackgroundRisk-adjusted cancer screening and prevention is a promising and continuously emerging option for improving cancer prevention. It is driven by increasing knowledge of risk factors and the ability to determine them for individual risk prediction. However, there is a knowledge gap between evidence of increased risk and evidence of the effectiveness and efficiency of clinical preventive interventions based on increased risk. This gap is, in particular, aggravated by the extensive availability of genetic risk factor diagnostics, since the question of appropriate preventive measures immediately arises when an increased risk is identified. However, collecting proof of effective preventive measures, ideally by prospective randomized preventive studies, typically requires very long periods of time, while the knowledge about an increased risk immediately creates a high demand for action.SummaryTherefore, we propose a risk-adjusted prevention concept that is based on the best current evidence making needed and appropriate preventive measures available, and which is constantly evaluated through outcome evaluation, and continuously improved based on these results. We further discuss the structural and procedural requirements as well as legal and socioeconomical aspects relevant for the implementation of this concept. 相似文献
148.
Joanna Kaczorowska Aurelija Cicilionyt Anne L. Timmerman Martin Deijs Maarten F. Jebbink Johannes B. van Goudoever Britt J. van Keulen Margreet Bakker Lia van der Hoek 《Viruses》2022,14(5)
Anelloviruses (AVs) are found in the vast majority of the human population and are most probably part of a healthy virome. These viruses infect humans in the early stage of life, however, the characteristics of the first colonizing AVs are still unknown. We screened a collection of 107 blood samples from children between 0.4 and 64.8 months of age for the presence of three AV genera: the Alpha-, Beta- and Gammatorquevirus. The youngest child that was positive for AV was 1.2 months old, and a peak in prevalence (100% of samples positive) was reached between the twelfth and eighteenth months of life. Intriguingly, the beta- and gammatorqueviruses were detected most at the early stage of life (up to 12 months), whereas alphatorqueviruses, the most common AVs in adults, increased in prevalence in children older than 12 months. To determine whether that order of colonization may be related to oral transmission and unequal presence of AV genera in breast milk, we examined 63 breast milk samples. Thirty-two percent of the breast milk samples were positive in a qPCR detecting beta- and gammatorqueviruses, while alphatorqueviruses were detected in 10% of the samples, and this difference was significant (p = 0.00654). In conclusion, we show that beta- and gammatorqueviruses colonize humans in the first months of life and that breastfeeding could play a role in AV transmission. 相似文献
149.
Florie E. van Beek Femke Jansen Rob J. Baatenburg de Jong Johannes A. Langendijk C. Ren Leemans Johannes H. Smit Robert P. Takes Chris H. J. Terhaard Jos A. E. Custers Judith B. Prins Birgit I. Lissenberg-Witte Irma M. Verdonck-de Leeuw 《Current oncology (Toronto, Ont.)》2022,29(5):3200
Background: To investigate associations between psychological problems and the use of healthcare and informal care and total costs among head and neck cancer (HNC) patients. Method: Data were used of the NETherlands QUality of Life and Biomedical Cohort study. Anxiety and depression disorder (diagnostic interview), distress, symptoms of anxiety and depression (HADS), and fear of cancer recurrence (FCR) and cancer worry scale (CWS) were measured at baseline and at 12-month follow-up. Care use and costs (questionnaire) were measured at baseline, 3-, 6-, 12-, and 24-month follow-up. Associations between psychological problems and care use/costs were investigated using logistic and multiple regression analyses. Results: Data of 558 patients were used. Distress, symptoms of anxiety or depression, FCR, and/or anxiety disorder at baseline were significantly associated with higher use of primary care, supportive care, and/or informal care (odds ratios (ORs) between 1.55 and 4.76). Symptoms of anxiety, FCR, and/or depression disorder at 12-month follow-up were significantly associated with use of primary care, supportive care, and/or informal care (ORs between 1.74 and 6.42). Distress, symptoms of anxiety, and FCR at baseline were associated with higher total costs. Discussion: HNC patients with psychological problems make more use of healthcare and informal care and have higher costs. This is not the result of worse clinical outcomes. 相似文献
150.
Jie Jin Wang Gabriëlle H.S. Buitendijk Elena Rochtchina Kristine E. Lee Barbara E.K. Klein Cornelia M. van Duijn Victoria M. Flood Stacy M. Meuer John Attia Chelsea Myers Elizabeth G. Holliday Ava G. Tan Wayne T. Smith Sudha K. Iyengar Paulus T.V.M. de Jong Albert Hofman Johannes R. Vingerling Paul Mitchell Ronald Klein Caroline C.W. Klaver 《Ophthalmology》2014