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71.
Bryan A. Bassig Xiao-Ou Shu Andreas Sjödin Woon-Puay Koh Yu-Tang Gao Jennifer Adams-Haduch Mark Davis Renwei Wang Yong-Bing Xiang Lawrence S. Engel Mark P. Purdue Bu-Tian Ji Gong Yang Richard S. Jones Hilde Langseth H. Dean Hosgood Tom K. Grimsrud Wei Jie Seow Jason Y.Y. Wong Wei Hu Dazhe Chen Wei Zheng Jian-Min Yuan Qing Lan Nathaniel Rothman 《International journal of cancer. Journal international du cancer》2020,146(3):839-849
Specific organochlorines (OCs) have been associated with non-Hodgkin lymphoma (NHL) with varying degrees of evidence. These associations have not been evaluated in Asia, where the high exposure and historical environmental contamination of certain OC pesticides (e.g., dichlorodiphenyltrichloroethane [DDT], hexachlorocyclohexane [HCH]) are different from Western populations. We evaluated NHL risk and prediagnostic blood levels of OC pesticides/metabolites and polychlorinated biphenyl congeners in a case–control study of 167 NHL cases and 167 controls nested within three prospective cohorts in Shanghai and Singapore. Conditional logistic regression was used to analyze lipid-adjusted OC levels and NHL risk. Median levels of p,p′-dichlorodiphenyldichloroethylene (p,p′-DDE), the primary DDT metabolite, and β-HCH were up to 12 and 65 times higher, respectively, in samples from the Asian cohorts compared to several cohorts in the United States and Norway. An increased risk of NHL was observed among those with higher β-HCH levels both overall (3rd vs. 1st tertile OR = 1.8, 95%CI = 1.0–3.2; ptrend = 0.049) and after excluding cases diagnosed within 2 years of blood collection (3rd vs. 1st tertile OR = 2.0, 95%CI = 1.1–3.9; ptrend = 0.03), and the association was highly consistent across the three cohorts. No significant associations were observed for other OCs, including p,p′-DDE. Our findings provide support for an association between β-HCH blood levels and NHL risk. This is a concern because substantial quantities of persistent, toxic residues of HCH are present in the environment worldwide. Although there is some evidence that DDT is associated with NHL, our findings for p,p′-DDE do not support an association. 相似文献
72.
Sanne C. F. A. Huijberts Robin M. J. M. van Geel Emilie M. J. van Brummelen Frans L. Opdam Serena Marchetti Neeltje Steeghs Saskia Pulleman Bas Thijssen Hilde Rosing Kim Monkhorst Alwin D. R. Huitema Jos H. Beijnen Ren Bernards Jan H. M. Schellens 《Cancer chemotherapy and pharmacology》2020,85(5):917-930
KRAS oncogene mutations cause sustained signaling through the MAPK pathway. Concurrent inhibition of MEK, EGFR, and HER2 resulted in complete inhibition of tumor growth in KRAS-mutant (KRASm) and PIK3CA wild-type tumors, in vitro and in vivo. In this phase I study, patients with advanced KRASm and PIK3CA wild-type colorectal cancer (CRC), non-small cell lung cancer (NSCLC), and pancreatic cancer, were treated with combined lapatinib and trametinib to assess the recommended phase 2 regimen (RP2R). Patients received escalating doses of continuous or intermittent once daily (QD) orally administered lapatinib and trametinib, starting at 750 mg and 1 mg continuously, respectively. Thirty-four patients (16 CRC, 15 NSCLC, three pancreatic cancers) were enrolled across six dose levels and eight patients experienced dose-limiting toxicities, including grade 3 diarrhea (n = 2), rash (n = 2), nausea (n = 1), multiple grade 2 toxicities (n = 1), and aspartate aminotransferase elevation (n = 1), resulting in the inability to receive 75% of planned doses (n = 2) or treatment delay (n = 2). The RP2R with continuous dosing was 750 mg lapatinib QD plus 1 mg trametinib QD and with intermittent dosing 750 mg lapatinib QD and trametinib 1.5 mg QD 5 days on/2 days off. Regression of target lesions was seen in 6 of the 24 patients evaluable for response, with one confirmed partial response in NSCLC. Pharmacokinetic results were as expected. Lapatinib and trametinib could be combined in an intermittent dosing schedule in patients with manageable toxicity. Preliminary signs of anti-tumor activity in NSCLC have been observed and pharmacodynamic target engagement was demonstrated. 相似文献
73.
Identification of Intellectual Disability Genes in Female Patients with a Skewed X‐Inactivation Pattern
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Nathalie Fieremans Hilde Van Esch Maureen Holvoet Gert Van Goethem Koenraad Devriendt Monica Rosello Sonia Mayo Francisco Martinez Shalini Jhangiani Donna M. Muzny Richard A. Gibbs James R. Lupski Joris R. Vermeesch Peter Marynen Guy Froyen 《Human mutation》2016,37(8):804-811
Intellectual disability (ID) is a heterogeneous disorder with an unknown molecular etiology in many cases. Previously, X‐linked ID (XLID) studies focused on males because of the hemizygous state of their X chromosome. Carrier females are generally unaffected because of the presence of a second normal allele, or inactivation of the mutant X chromosome in most of their cells (skewing). However, in female ID patients, we hypothesized that the presence of skewing of X‐inactivation would be an indicator for an X chromosomal ID cause. We analyzed the X‐inactivation patterns of 288 females with ID, and found that 22 (7.6%) had extreme skewing (>90%), which is significantly higher than observed in the general population (3.6%; P = 0.029). Whole‐exome sequencing of 19 females with extreme skewing revealed causal variants in six females in the XLID genes DDX3X, NHS, WDR45, MECP2, and SMC1A. Interestingly, variants in genes escaping X‐inactivation presumably cause both XLID and skewing of X‐inactivation in three of these patients. Moreover, variants likely accounting for skewing only were detected in MED12, HDAC8, and TAF9B. All tested candidate causative variants were de novo events. Hence, extreme skewing is a good indicator for the presence of X‐linked variants in female patients. 相似文献
74.
Pheochromocytomas and paragangliomas are neuroendocrine neoplasias of neural crest origin. Genetic mutations that are characterized
in other human neoplasms are rarely seen in these tumors. About 10% of the patients with pheochromocytomas and paragangliomas
present with a family history of von Hippel-Lindau disease (VHL), Multiple endocrine neoplasia type 2 (MEN2), one of the three
familial paraganglioma syndromes (PGL; PGL1, PGL3, PGL4), or neurofibromatosis type 1 (NF1). In an even higher percentage,
a genetic predisposition is involved in the development of these tumors. The genes of hereditary tumor syndromes such as the
aforementioned ones are also ideal to study the molecular pathogenesis in the sporadic counterparts. Many studies have been
undertaken to identify important secondary genetic events that contribute to the tumorigenesis of pheochromocytoma or paraganglioma,
but a comprehensive review of these data is lacking. Recent findings of CGH and LOH studies provided new starting points to
unravel the pathogenesis and progression of these tumors. This review presents an overview of our current understanding of
the molecular pathogenesis of pheochromocytoma and paraganglioma.
This work has been presented at the Endocrine Pathology Society meeting of the 92nd annual USCAP meeting in Washington DC,
March 22, 2003. 相似文献
75.
Marta?Ferrer Isabelle?Boccon-Gibod Margarida?Gon?alo Hüseyin?Serhat??nal?z André?Knulst Hilde?Lapeere Anchala?Parthasaradhi Georg?Stingl Anna?Tagka Fernando?Valenzuela Jensen?Yeung Simon?Francis?ThomsenEmail author 《European journal of dermatology : EJD》2017,27(5):455-463
Omalizumab (a recombinant, humanized anti-immunoglobulin-E anti-body) has been shown in three pivotal Phase III trials (ASTERIA I, II and GLACIAL) and real-world studies to be effective and well-tolerated for the treatment of chronic spontaneous urticaria (CSU), and is the only licensed third-line treatment for CSU. However, the definition of response to omalizumab treatment often differs between clinical trials, real-world studies, and daily practice of individual physicians globally. As such, a consensus definition of “complete”, “partial” and “non-response” to omalizumab is required in order to harmonize treatment management and compare data. Here, it is proposed that a disease measurement tool, for example, the 7-Day Urticaria Activity Score (UAS7) or Urticaria Control Test (UCT) is required for defining response. The addition of quality of life measurements is helpful to gain insight into a patient’s disease burden and its changes during treatment. A potential omalizumab treatment approach based on speed and pattern of response at 1-3 and 3-6 months is suggested. In cases where there is no response during the first 1-3 months, physicians should consider reassessing the original CSU diagnosis. Moreover, in patients showing partial response at 12 weeks, treatment with omalizumab should be continued in order to maximize the possibility of achieving symptom control. If patients have a UAS7>6 and/or UCT<12, then continued treatment is advised, dependent on physician judgement and patient expectations. In treatment responders, omalizumab treatment can be resumed at a later stage after discontinuation with the same degree of symptom control. 相似文献
76.
Hilde M. Norum Annika E. Michelsen Tove Lekva Satish Arora Kari Otterdal Maria Belland Olsen Xiang Yi Kong Einar Gude Arne K. Andreassen Dag Solbu Kristjan Karason Gran Dellgren Lars Gullestad Pl Aukrust Thor Ueland 《American journal of transplantation》2019,19(4):1050-1060
Cardiac allograft vasculopathy (CAV) causes heart failure after heart transplantation (HTx), but its pathogenesis is incompletely understood. Notch signaling, possibly modulated by everolimus (EVR), is essential for processes involved in CAV. We hypothesized that circulating Notch ligands would be dysregulated after HTx. We studied circulating delta‐like Notch ligand 1 (DLL1) and periostin (POSTN) and CAV in de novo HTx recipients (n = 70) randomized to standard or EVR‐based, calcineurin inhibitor‐free immunosuppression and in maintenance HTx recipients (n = 41). Compared to healthy controls, plasma DLL1 and POSTN were elevated in de novo (P < .01; P < .001) and maintenance HTx recipients (P < .001; P < .01). Use of EVR was associated with a treatment effect for DLL1. For de novo HTx recipients, a change in DLL1 correlated with a change in CAV at 1 (P = .021) and 3 years (P = .005). In vitro, activation of T cells increased DLL1 secretion, attenuated by EVR. In vitro data suggest that also endothelial cells and vascular smooth muscle cells (VSMCs) could contribute to circulating DLL1. Immunostaining of myocardial specimens showed colocalization of DLL1 with T cells, endothelial cells, and VSMCs. Our findings suggest a role of DLL1 in CAV progression, and that the beneficial effect of EVR on CAV could reflect a suppressive effect on DLL1. Trial registration numbers— SCHEDULE trial: ClinicalTrials.gov NCT01266148; NOCTET trial: ClinicalTrials.gov NCT00377962. 相似文献
77.
Changes in vaulting of myopic and toric implantable collamer lenses in different lighting conditions
Are Lindland Hilde Heger Maria Kugelberg Charlotta Zetterström 《Acta ophthalmologica. Supplement》2012,90(8):788-791
Purpose: To evaluate the changes in vaulting of myopic and toric Implantable Collamer Lenses (ICLs) in different lighting conditions. Methods: Thirty‐seven eyes of 37 patients implanted with a myopic ICL and 26 eyes of 26 patients implanted with a toric ICL were examined using Visante optical coherence tomography (OCT) in photopic (257 lux) and mesopic (2 lux) conditions. Pupil diameter and distance changes between the ICL and adjacent intraocular structures were measured. Results: The mean horizontal pupillary diameters in mesopic conditions were 5.3 ± 0.9 (SD) mm. In photopic conditions, a mean decrease of –1.8 ± 0.6 mm [95% confidence interval (95% CI) ?2.0 to ?1.7; p < 0.0001] was observed. The mean distances between the ICL and the crystalline lens in mesopic conditions were 0.33 ± 0.17 mm. In photopic conditions, a mean decrease of ?0.04 ± 0.06 mm (95% CI ?0.05 to ?0.02; p < 0.0001) in the ICL‐crystalline lens distance was found. There was a ?0.02 ± 0.04 mm (95% CI ?0.03 to ?0.01; p = 0.0022) decrease in the anterior chamber depth and a 0.02 ± 0.06 mm (95% CI 0.002 to 0.032; p = 0.0275) increase in the distance between the cornea and the ICL. We found no difference in the change in vaulting between the two ICLs in different lighting conditions. Conclusion: There is a decrease in the central vaulting of myopic and toric ICLs in photopic conditions. This is due to both posterior movement of the ICL and anterior protrusion of the crystalline lens. 相似文献
78.
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80.
ObjectiveTo describe patients’ experiences when diagnosed with psychogenic non-epileptic seizures (PNES).MethodsThe study was based on in-depth interviews with ten patients, previously diagnosed with epilepsy and treated with antiepileptic drugs (AEDs) whose seizures were subsequently defined as PNES. The empirical material was analyzed by systematic text condensing strategies within the interpretative tradition.ResultsSwitch in diagnosis was demanding, both cognitively and emotionally. The patients had difficulty understanding the diagnosis. When the cause of the seizures was unclear, this resulted in feelings of hopelessness and helplessness, a need for re-evaluation of self-understanding, and increased levels of patient stress. The patients felt that with the change in diagnosis, responsibility was transferred from the health authorities to themselves.ConclusionsThe mode of communicating the PNES diagnosis may be decisive for the patients’ treatment motivation and ability to cope with the disorder. In order to avoid the patients feeling that they have been abandoned with a difficult diagnosis, close cooperation between neurologists and psychiatrists is essential. 相似文献