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41.
Molecular mechanisms of metastasis 总被引:8,自引:0,他引:8
Hoon DS Kitago M Kim J Mori T Piris A Szyfelbein K Mihm MC Nathanson SD Padera TP Chambers AF Vantyghem SA MacDonald IC Shivers SC Alsarraj M Reintgen DS Passlick B Sienel W Pantel K 《Cancer metastasis reviews》2006,25(2):203-220
A major topic covered at the First International Symposium on Cancer Metastasis and the Lymphovascular System was the molecular
mechanisms of metastasis. This has become of major interest in recent years as we have discovered new metastasis-related genes
and gained understanding of the molecular events of lymphatic metastasis. The symposium covered new aspects and important
questions related to the events of metastasis in both humans and animals. The basic and clinical related research covered
in this topic represented many disciplines. The presentations showed novel findings and at the same time, raised many new
unanswered questions, indicating the limited knowledge we still have regarding the molecular events of metastasis. The hope
is that further unraveling of the direct and indirect molecular events of lymphatic metastasis will lead to new approaches
in developing effective therapeutics.
Presented as Session III of the First International Symposium on Cancer Metastasis and the Lymphovascular System. April 28–30,
2005, San Francisco, CA; Chaired by Dave S.B. Hoon. 相似文献
42.
Christensen MS Heyman M Möttönen M Zeller B Jonmundsson G Hasle H;Nordic Society of Paediatric Haematology Oncology 《British journal of haematology》2005,131(1):50-58
Despite continuously more successful treatment of childhood acute lymphoblastic leukaemia (ALL), 2-5% of children still die of other causes than relapse. The Nordic Society of Paediatric Haematology and Oncology-ALL92 protocol included 1652 patients < or =15 years of age with precursor B- and T-cell ALL diagnosed between 1992 and 2001. Induction deaths and deaths in first complete remission (CR1) were included in the study. A total of 56 deaths (3%) were identified: 19 died during induction (1%) and 37 in CR1 (2%). Infection was the major cause of death in 38 cases. Five patients died of early death before initiation of cytotoxic therapy. Five patients died because of toxicity of inner organs and one of accidental procedure failures. Seven patients died of complications following allogenic haematopoietic stem cell transplantation (HSCT) in CR1. Girls were at higher risk of treatment-related death (TRD) [relative risk (RR) = 2.2; 95% confidence interval (CI(95%)): 1.2-4.0, P < 0.01], mostly because of infections. Risk of TRD was also higher in children with Down syndrome (RR = 4.5; CI(95%): 2.0-10.2, P < 0.00). In conclusion, 3% of children with ALL died of TRD, with bacterial infections as the most common cause of death. Girls and Down syndrome patients had a higher risk of TRD. Infections still remain a major challenge in childhood ALL. 相似文献
43.
Julia Diemer Katharina Domschke Andreas Mühlberger Bernward Winter Maxim Zavorotnyy Swantje Notzon Karen Silling Volker Arolt Peter Zwanzger 《European neuropsychopharmacology》2013,23(11):1551-1560
Anxiety disorders are among the most frequent psychiatric disorders. With regard to pharmacological treatment, antidepressants, the calcium modulator pregabalin and benzodiazepines are recommended according to current treatment guidelines. With regard to acute states of anxiety, so far practically only benzodiazepines provide an immediate anxiolytic effect. However, the risk of tolerance and dependency limits the use of this class of medication. Therefore, there is still a need for alternative pharmacologic strategies. Increasing evidence points towards anxiety-reducing properties of atypical antipsychotics, particularly quetiapine. Therefore, we aimed to evaluate the putative acute anxiolytic effects of this compound, choosing the induction of acute anxiety in patients with specific phobia as a model for the evaluation of ad-hoc anxiolytic properties in a proof-of-concept approach. In a randomized, double-blind, placebo-controlled study, 58 patients with arachnophobia were treated with a single dose of quetiapine XR or placebo prior to a virtual reality spider challenge procedure. Treatment effects were monitored using rating scales for acute anxiety as well as measurements of heart rate and skin conductance. Overall, quetiapine showed significant anxiolytic effects compared to placebo. However, effects were not seen on the primary outcome measure (VAS Anxiety), but were limited to somatic anxiety symptoms. Additionally, a significant reduction of skin conductance was observed. Further exploratory analyses hint towards a mediating role of the (COMT) val158met genotype on treatment response. The present results thus suggest a possible suitability of quetiapine in the acute treatment of anxiety, particularly with regard to somatic symptoms. 相似文献
44.
Paules RS Aubrecht J Corvi R Garthoff B Kleinjans JC 《Environmental health perspectives》2011,119(6):739-743
Background
The current safety paradigm for assessing carcinogenic properties of drugs, cosmetics, industrial chemicals, and environmental exposures relies mainly on in vitro genotoxicity testing followed by 2-year rodent bioassays. This testing battery is extremely sensitive but has low specificity. Furthermore, rodent bioassays are associated with high costs, high animal burden, and limited predictive value for human risks.Objectives
We provide a response to a growing appeal for a paradigm change in human cancer risk assessment.Methods
To facilitate development of a road map for this needed paradigm change in carcinogenicity testing, a workshop titled “Genomics in Cancer Risk Assessment” brought together toxicologists from academia and industry and government regulators and risk assessors from the United States and the European Union. Participants discussed the state-of-the-art in developing alternative testing strategies for carcinogenicity, with emphasis on potential contributions from omics technologies.Results and Conclusions
The goal of human risk assessment is to decide whether a given exposure to an agent is acceptable to human health and to provide risk management measures based on evaluating and predicting the effects of exposures on human health. Although exciting progress is being made using genomics approaches, a new paradigm that uses these methods and human material when possible would provide mechanistic insights that may inform new predictive approaches (e.g., in vitro assays) and facilitate the development of genomics-derived biomarkers. Regulators appear to be willing to accept such approaches where use is clearly defined, evidence is strong, and approaches are qualified for regulatory use. 相似文献45.
Background:
Congenital left ventricular aneurysm (LVA) and diverticulum (LVD) are rare cardiac anomalies and frequently associated with other cardiac anomalies. The objective of our study was to investigate the prevalence and the spectrum of coronary anomalies in such patients.Hypothesis:
The incidence of coronary anomalies is increased in patients with LVA or LVD.Methods:
We assessed 117 patients with isolated LVA or LVD for the prevalence of coronary anomalies and compared the findings with an age‐ and sex‐matched control group (n = 117) without the diagnosis of LVA or LVD.Results:
Coronary anomalies were present in 58.1% of the study population (68 of 117). The median age of affected patients was 64 years, and 45 (38.5%) were male. Coronary anomalies were more prevalent in patients with LVA or LVD (58.1% vs 6.8%, P < 0.001), male patients (89% vs 57%, P = 0.0002), and in patients with nonapical location of LVA or LVD (24% vs 45%, P = 0.02) compared with control, whereas age and type (LVA vs LVD) had no influence (57% vs 57.6%, P = 0.4; and 58.8% vs 57.6%, P = 0.87, respectively). The number of adverse cardiac events was similar in both groups during a 4.2‐year follow‐up period (29% vs 19%, P = 0.09). None of the patients in our series had major coronary anomalies with potential lethal consequences.Conclusions:
This large single‐center study suggests that the prevalence of abnormal coronary‐artery anatomy in patients with isolated LVA or LVD is as high as 58.1%. However, we did not identify major coronary anomalies with potential lethal consequences, and the clinical course during follow‐up was not influenced by the presence or absence of coronary anomalies. © 2011 Wiley Periodicals, Inc. The authors have no funding, financial relationships, or conflicts of interest to disclose. 相似文献46.
47.
48.
49.
Anne Cathrine Lund Laursen Julie Damgaard Sandahl Eigil Kjeldsen Jonas Abrahamsson Peter Asdahl Shau‐Yin Ha Jesper Heldrup Kirsi Jahnukainen Ólafur G. Jónsson Birgitte Lausen Josefine Palle Bernward Zeller Erik Forestier Henrik Hasle 《Genes, chromosomes & cancer》2016,55(9):719-726
Trisomy 8 (+8) is a common cytogenetic aberration in acute myeloid leukemia (AML); however, the impact of +8 in pediatric AML is largely unknown. We retrospectively investigated 609 patients from the NOPHO‐AML database to determine the clinical and cytogenetic characteristics of +8 in pediatric AML and to investigate its prognostic impact. Complete cytogenetic data were available in 596 patients (98%) aged 0–18 years, diagnosed from 1993 to 2012, and treated according to the NOPHO‐AML 1993 and 2004 protocols in the Nordic countries and Hong Kong. We identified 86 patients (14%) with +8. Trisomy 8 was combined with other cytogenetic aberrations in 68 patients (11%) (+8 other) and in 18 patients (3%), it was the sole abnormality (+8 alone). Trisomy 8 was associated with FAB M5 (36%) but otherwise clinically comparable with non‐trisomy 8 patients. Trisomy 8 was favorable in patients of young age and with t(9;11). Trisomy 8 alone was associated with older age (median age 10.1 years), FAB M2 (33%), and FLT3‐ITD mutations (58%). The 5‐year event‐free survival for patients with +8 alone was 50% and 5‐year overall survival was 75%. In conclusion, +8 is one of the most common cytogenetic aberrations in pediatric AML. Trisomy 8 positive AML is a heterogeneous group and the majority of cases have additional cytogenetic aberrations. Patients with +8 alone differed from patients with +8 other and were associated with older age, FAB M2, and FLT3‐ITD aberrations. There were no differences in survival despite the more frequent occurrence of FLT3‐ITD in +8 alone. © 2016 Wiley Periodicals, Inc. 相似文献
50.
Domschke K Klauke B Winter B Gajewska A Herrmann MJ Warrings B Mühlberger A Wosnitza K Dlugos A Naunin S Nienhaus K Fobker M Jacob C Arolt V Pauli P Reif A Zwanzger P Deckert J 《Psychopharmacology》2012,222(3):533-541