Refine
Year of publication
Document Type
- Journal article (7538) (remove)
Language
- English (7538) (remove)
Keywords
- Toxikologie (110)
- Medizin (94)
- inflammation (86)
- Biochemie (81)
- Anorganische Chemie (66)
- cancer (64)
- gene expression (62)
- Organische Chemie (59)
- Infektionsbiologie (57)
- apoptosis (53)
Institute
- Theodor-Boveri-Institut für Biowissenschaften (1332)
- Physikalisches Institut (360)
- Institut für Psychologie (354)
- Neurologische Klinik und Poliklinik (343)
- Medizinische Klinik und Poliklinik II (339)
- Medizinische Klinik und Poliklinik I (330)
- Institut für Molekulare Infektionsbiologie (297)
- Institut für Anorganische Chemie (252)
- Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie (245)
- Institut für Organische Chemie (234)
Sonstige beteiligte Institutionen
- Johns Hopkins School of Medicine (11)
- IZKF Nachwuchsgruppe Geweberegeneration für muskuloskelettale Erkrankungen (7)
- Clinical Trial Center (CTC) / Zentrale für Klinische Studien Würzburg (ZKSW) (5)
- Wilhelm-Conrad-Röntgen-Forschungszentrum für komplexe Materialsysteme (5)
- Bernhard-Heine-Centrum für Bewegungsforschung (4)
- Johns Hopkins University School of Medicine (4)
- Zentraleinheit Klinische Massenspektrometrie (4)
- Center for Interdisciplinary Clinical Research, Würzburg University, Würzburg, Germany (2)
- Interdisciplinary Center for Clinical Research (2)
- Interdisziplinäres Zentrum für Klinische Forschung (IZKF) (2)
ResearcherID
- D-1221-2009 (1)
Background
Although Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations in the α-galactosidase A gene (GLA), women may develop severe symptoms. We investigated X-chromosomal inactivation patterns (XCI) as a potential determinant of symptom severity in FD women.
Patients and Methods
We included 95 women with mutations in GLA (n = 18 with variants of unknown pathogenicity) and 50 related men, and collected mouth epithelial cells, venous blood, and skin fibroblasts for XCI analysis using the methylation status of the androgen receptor gene. The mutated X-chromosome was identified by comparison of samples from relatives. Patients underwent genotype categorization and deep clinical phenotyping of symptom severity.
Results
43/95 (45%) women carried mutations categorized as classic. The XCI pattern was skewed (i.e., ≥75:25% distribution) in 6/87 (7%) mouth epithelial cell samples, 31/88 (35%) blood samples, and 9/27 (33%) skin fibroblast samples. Clinical phenotype, α-galactosidase A (GAL) activity, and lyso-Gb3 levels did not show intergroup differences when stratified for X-chromosomal skewing and activity status of the mutated X-chromosome.
Conclusions
X-inactivation patterns alone do not reliably reflect the clinical phenotype of women with FD when investigated in biomaterial not directly affected by FD. However, while XCI patterns may vary between tissues, blood frequently shows skewing of XCI patterns.
Background
Xiphophorus fishes are represented by 26 live-bearing species of tropical fish that express many attributes (e.g., viviparity, genetic and phenotypic variation, ecological adaptation, varied sexual developmental mechanisms, ability to produce fertile interspecies hybrids) that have made attractive research models for over 85 years. Use of various interspecies hybrids to investigate the genetics underlying spontaneous and induced tumorigenesis has resulted in the development and maintenance of pedigreed Xiphophorus lines specifically bred for research. The recent availability of the X. maculatus reference genome assembly now provides unprecedented opportunities for novel and exciting comparative research studies among Xiphophorus species.
Results
We present sequencing, assembly and annotation of two new genomes representing Xiphophorus couchianus and Xiphophorus hellerii. The final X. couchianus and X. hellerii assemblies have total sizes of 708 Mb and 734 Mb and correspond to 98 % and 102 % of the X. maculatus Jp 163 A genome size, respectively. The rates of single nucleotide change range from 1 per 52 bp to 1 per 69 bp among the three genomes and the impact of putatively damaging variants are presented. In addition, a survey of transposable elements allowed us to deduce an ancestral TE landscape, uncovered potential active TEs and document a recent burst of TEs during evolution of this genus.
Conclusions
Two new Xiphophorus genomes and their corresponding transcriptomes were efficiently assembled, the former using a novel guided assembly approach. Three assembled genome sequences within this single vertebrate order of new world live-bearing fishes will accelerate our understanding of relationship between environmental adaptation and genome evolution. In addition, these genome resources provide capability to determine allele specific gene regulation among interspecies hybrids produced by crossing any of the three species that are known to produce progeny predisposed to tumor development.
Mutations in the oncogenic PIK3CA gene are found in 10-20% of colorectal cancers (CRCs) and are associated with poor prognosis. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and agonistic TRAIL death receptor antibodies emerged as promising anti-neoplastic therapeutics, but to date failed to prove their capability in the clinical setting as especially primary tumors exhibit high rates of TRAIL resistance. In our study, we investigated the molecular mechanisms underlying TRAIL resistance in CRC cells with a mutant PIK3CA (PIK3CA-mut) gene. We show that inhibition of the constitutively active phosphatidylinositol-3 kinase (PI3K)/Akt signaling pathway only partially overcame TRAIL resistance in PIK3CA-mut-protected HCT116 cells, although synergistic effects of TRAIL plus PI3K, Akt or cyclin-dependent kinase (CDK) inhibitors could be noted. In sharp contrast, TRAIL triggered full-blown cell death induction in HCT116 PIK3CA-mut cells treated with proteasome inhibitors such as bortezomib and MG132. At the molecular level, resistance of HCT116 PIK3CA-mut cells against TRAIL was reflected by impaired caspase-3 activation and we provide evidence for a crucial involvement of the E3-ligase X-linked inhibitor of apoptosis protein (XIAP) therein. Drugs interfering with the activity and/or the expression of XIAP, such as the second mitochondria-derived activator of caspase mimetic BV6 and mithramycin-A, completely restored TRAIL sensitivity in PIK3CA-mut-protected HCT116 cells independent of a functional mitochondrial cell death pathway. Importantly, proteasome inhibitors and XIAP-targeting agents also sensitized other CRC cell lines with mutated PIK3CA for TRAIL-induced cell death. Together, our data suggest that proteasome-or XIAP-targeting drugs offer a novel therapeutic approach to overcome TRAIL resistance in PIK3CA-mutated CRC.
The Xiphophorus tumor system has provided the opportunity to reduce the enormous complexity of cancer etiology to a few biological elements basically involved in neoplasia. The development of a tumor requires an oncogene which, after impairment, deletion, or elimination of its regulatory genes is permitted to mediate neoplastic transformation. Emphasis is being placed today in cancer research on the actual oncogenes themselves, but, in our opinion, the most important genes involved in neoplasia are these regulatory genes. However, although detected by c1assical genetics in the Xiphophorus system, th ese genes are not at present open to a more fin ely detailed molecular biological analysis. Their actual mode of action is therefore still far from being understood.
Xmrk encodes a putative transmembrane glycoprotein of the tyrosine kinase family and is a melanoma-inducing gene in Xiphophorus. We attempted to investigate the biological function of the putative Xmrk receptor by characterizing its signalling properties. Since a potential Iigand for Xmrk has not yet been identified, it has been difficult to analyse the biochemical properlies and biological function of this cell surface protein. In an approach towards such analyses, the Xmrk extracellular domain was replaced by the closely related Iigand-binding domain sequences of the human epidennal growth factor receptor (HER) and the ligand-induced activity of the chimeric HER-Xmrk proteinwas examined. We show that the Xmrk protein is a functional receptor tyrosine kinase, is highly active in malignant melanoma and displays a constitutive autophosphorylation activity possibly due to an activating mutation in its extracellular or transmembrane domain. In the focus formation assay the HER-Xmrk chimera is a potent transfonning protein equivalent to other tyrosine kinase oncoproteins.
Phosphines are important ligands in homogenous catalysis and have been crucial for many advances, such as in cross-coupling, hydrofunctionalization, or hydrogenation reactions. Herein we report the synthesis and application of a novel class of phosphines bearing ylide substituents. These phosphines are easily accessible via different synthetic routes from commercially available starting materials. Owing to the extra donation from the ylide group to the phosphorus center the ligands are unusually electron-rich and can thus function as strong electron donors. The donor capacity surpasses that of commonly used phosphines and carbenes and can easily be tuned by changing the substitution pattern at the ylidic carbon atom. The huge potential of ylide-functionalized phosphines in catalysis is demonstrated by their use in gold catalysis. Excellent performance at low catalyst loadings under mild reaction conditions is thus seen in different types of transformations.
Purpose
Examine the effects of an 8-week yoga therapy on fatigue in patients with different types of cancer.
Methods
A total of 173 cancer patients suffering from mild to severe fatigue were randomly allocated to yoga intervention (n = 84) (IG) versus waitlist control group (CG) (n = 88). Yoga therapy consisted of eight weekly sessions with 60 min each. The primary outcome was self-reported fatigue symptoms. Secondary outcomes were symptoms of depression and quality of life (QoL). Data were assessed using questionnaires before (T0) and after yoga therapy for IG versus waiting period for CG (T1).
Results
A stronger reduction of general fatigue (P = .033), physical fatigue (P = .048), and depression (P < .001) as well as a stronger increase in QoL (P = .002) was found for patients who attended 7 or 8 sessions compared with controls. Within the yoga group, both higher attendance rate and lower T0-fatigue were significant predictors of lower T1-fatigue (P ≤ .001). Exploratory results revealed that women with breast cancer report a higher reduction of fatigue than women with other types of cancer (P = .016) after yoga therapy.
Conclusion
The findings support the assumption that yoga therapy is useful to reduce cancer-related fatigue, especially for the physical aspects of fatigue. Women with breast cancer seem to benefit most, and higher attendance rate results in greater reduction of fatigue.
Trial registration
German Clinical Trials Register DRKS00016034
Background
Almost 90% of cancer patients suffer from symptoms of fatigue during treatment. Supporting treatments are increasingly used to alleviate the burden of fatigue. This study examines the short-term and long-term effects of yoga on fatigue and the effect of weekly reminder e-mails on exercise frequency and fatigue symptoms.
Methods
The aim of the first part of the study will evaluate the effectiveness of yoga for cancer patients with mixed diagnoses reporting fatigue. We will randomly allocate 128 patients to an intervention group (N = 64) receiving yoga and a wait-list control group (N = 64) receiving yoga 9 weeks later. The yoga therapy will be performed in weekly sessions of 60 min each for 8 weeks. The primary outcome will be self-reported fatigue symptoms. In the second part of the study, the effectiveness of reminder e-mails with regard to the exercise frequency and self-reported fatigue symptoms will be evaluated. A randomized allocated group of the participants (“email”) receives weekly reminder e-mails, the other group does not. Data will be assessed using questionnaires the beginning and after yoga therapy as well as after 6 months.
Discussion
Support of patients suffering from fatigue is an important goal in cancer patients care. If yoga therapy will reduce fatigue, this type of therapy may be introduced into routine practice. If the reminder e-mails prove to be helpful, new offers for patients may also develop from this.
Objective
To examine the efficacy of reminder e-mails to continue yoga therapy on practice frequency and fatigue in cancer patients and long-term effects of yoga on fatigue, depression, and quality of life.
Methology
One hundred two cancer patients who completed an 8-week yoga therapy were randomly allocated to two groups: reminder (N = 51) vs. no-reminder group (N = 51). After completing yoga therapy, the reminder group received weekly e-mails for 24 weeks, which reminded them of practicing yoga, whereas the no-reminder group did not. Primary outcomes were fatigue and practice frequency, and long-term outcomes were fatigue, depression, and quality of life. Data were assessed using questionnaires after yoga therapy (T1) and 6 months after completing yoga therapy (T2).
Result
A significantly stronger reduction of general (p = 0.038, d = 0.42) and emotional fatigue (p = 0.004, d = 0.59) and a higher increase of practice frequency (p = 0.015, d = 0.52) between T1 and T2 were found for the reminder group compared to the no-reminder group. In the mediation model, practice frequency as a mediator partially explained the changes in emotional fatigue (indirect effect B = - 0.10). Long-term effects of yoga therapy regarding fatigue, depression, and quality of life were found (F > 7.46, p < 0.001, d > 0.54).
Conclusion
Weekly reminder e-mails after yoga therapy can positively affect general and emotional fatigue and help cancer patients with fatigue establish a regular yoga practice at home. However, higher practice frequency did not lead to higher physical or cognitive fatigue improvement, suggesting other factors that mediate efficacy on physical or cognitive fatigue, such as mindfulness or side effects of therapy.