Health-Related Quality of Life Outcomes from Botulinum Toxin Treatment in Spasticity.

Objective: The effects of botulinum toxin injections (BoNT) on health-related quality of life along the complex spectrum of spasticity needs further characterization to guide practitioners in a real-life therapeutic environment.

Methods: In this study, we analyzed 50 consecutive and unselected patients with spasticity before and four weeks after re-injection of botulinum toxin. Health-related quality of life in terms of the EuroQol (EQ) as well as further motor and non-motor characteristics were assessed.

Health-related quality of life outcomes from botulinumtoxin treatment in blepharospasm.

Objective: Blepharospasm associates with impairment in generic health-related quality of life (HR-QoL). Albeit botulinum toxin is widely used to alleviate the motor symptoms of blepharospasm, its effect on generic health-related quality of life (HR-QoL) is heterogeneous.

Patients And Methods: In this open-label clinical observational study, we characterized outcomes on HR-QoL in terms of the EuroQol (EQ-5D-5 L) from botulinum toxin (BoNT) injection in a prospective cohort of patients with blepharospasm (n = 55).

Botulinumtoxin Improves both Generic and Disease-Specific Quality of Life in Cervical Dystonia.

Botulinumtoxin injection (BoNT) into affected muscles is effective to improve motor symptoms of cervical dystonia (CD) by reducing muscle contraction and involuntary dystonic movement and posturing. However, the understanding of the effect on health-related quality of life (HR-QoL) and patient referral under HR-QoL aspects is incomplete. In this open-label clinical prospective observational study, we characterized the outcomes in CD ( = 159) from botulinumtoxin on both generic HR-QoL (EuroQol; EQ-5D-5L) and disease-specific HR-QoL [craniocervical dystonia questionnaire (CDQ-24)].

Health-related quality of life outcomes from botulinum toxin treatment in hemifacial spasm.

Background: Although botulinum neurotoxin (BoNT) injections may alleviate involuntary muscle contractions in hemifacial spasm substantially, it is less clear whether the motor effect would translate into improvements of health-related quality of life (HR-QoL).

Methods: In this open-label clinical observational study, we characterized outcomes on HR-QoL in terms of the EuroQol (EQ-5D-5L) from BoNT in a prospective cohort of patients with hemifacial spasm ( = 73). Additionally, we characterized appendicular motor and nonmotor signs on motor symptom improvement, depressive symptoms, pain and sleep quality.

Genomic amplification of Fanconi anemia complementation group A (FancA) in head and neck squamous cell carcinoma (HNSCC): Cellular mechanisms of radioresistance and clinical relevance.

Radio (chemo) therapy is a crucial treatment modality for head and neck squamous cell carcinoma (HNSCC), but relapse is frequent, and the underlying mechanisms remain largely elusive. Therefore, novel biomarkers are urgently needed. Previously, we identified gains on 16q23-24 to be associated with amplification of the Fanconi anemia A (FancA) gene and to correlate with reduced progression-free survival after radiotherapy.

Integrative analysis of the microRNA-mRNA response to radiochemotherapy in primary head and neck squamous cell carcinoma cells.

Background: Head and neck squamous cell carcinoma (HNSCC) is a very heterogeneous disease resulting in huge differences in the treatment response. New individualized therapy strategies including molecular targeting might help to improve treatment success. In order to identify potential targets, we developed a HNSCC radiochemotherapy cell culture model of primary HNSCC cells derived from two different patients (HN1957 and HN2092) and applied an integrative microRNA (miRNA) and mRNA analysis in order to gain information on the biological networks and processes of the cellular therapy response.

TCDD induces the expression of insulin-like growth factor binding protein 4 in 5L rat hepatoma cells: a cautionary tale of the use of this cell line in studies on dioxin toxicity.

Previous quantitative proteomic studies on the actions of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in 5L rat hepatoma cells, a cell model frequently used for investigating the mechanisms of TCDD toxicity, had indicated that dioxin exposure reduced the abundance of numerous proteins which are regulated at the level of protein synthesis initiation. In the present study, we have analysed the mechanism mediating this inhibition. TCDD treatment of the cells largely prevented the activation of eukaryotic translation initiation factor 4E-binding protein 1, a regulator of translation initiation and substrate of the mammalian target of rapamycin (mTOR).

Feedback-dependent generalization.

Generalization provides a window into the representational changes that occur during motor learning. Neural network models have been integral in revealing how the neural representation constrains the extent of generalization. Specifically, two key features are thought to define the pattern of generalization.

Proteomic analysis by SILAC and 2D-DIGE reveals radiation-induced endothelial response: four key pathways.

Epidemiological data show that ionising radiation increases the risk of cardiovascular disease. The endothelium is one of the main targets of radiation-induced damage. Rapid radiation-induced alterations in the biological processes were investigated after exposure to a clinically relevant radiation dose (2.

Delineating chromosomal breakpoints in radiation-induced papillary thyroid cancer.

Recurrent translocations are well known hallmarks of many human solid tumors and hematological disorders, where patient- and breakpoint-specific information may facilitate prognostication and individualized therapy. In thyroid carcinomas, the proto-oncogenes RET and NTRK1 are often found to be activated through chromosomal rearrangements. However, many sporadic tumors and papillary thyroid carcinomas (PTCs) arising in patients with a history of exposure to elevated levels of ionizing irradiation do not carry these known abnormalities.

Chromosomal rearrangements in post-Chernobyl papillary thyroid carcinomas: evaluation by spectral karyotyping and automated interphase FISH.

Structural genomic rearrangements are frequent findings in human cancers. Therefore, papillary thyroid carcinomas (PTCs) were investigated for chromosomal aberrations and rearrangements of the RET proto-oncogene. For this purpose, primary cultures from 23 PTC have been established and metaphase preparations were analysed by spectral karyotyping (SKY).

Novel human prostate cell lines derived from the transition and peripheral zones of the prostate for carcinogenesis studies.

Epithelial cell lines were established from the transition and peripheral zones of human prostate by transduction with cdk4 and hTERT. The properties of these lines were investigated using immunocytochemical markers, ability to generate anchorage-independent colonies and by spectral karyotyping (SKY). Cells were exposed to fractionated doses of gamma irradiation to investigate their ability to transform.

Establishment and Molecular Cytogenetic Characterization of a Cell Culture Model of Head and Neck Squamous Cell Carcinoma (HNSCC).

Cytogenetic analysis of head and neck squamous cell carcinoma (HNSCC) established several biomarkers that have been correlated to clinical parameters during the past years. Adequate cell culture model systems are required for functional studies investigating those potential prognostic markers in HNSCC. We have used a cell line, CAL 33, for the establishment of a cell culture model in order to perform functional analyses of interesting candidate genes and proteins.

Novel gene rearrangements in transformed breast cells identified by high-resolution breakpoint analysis of chromosomal aberrations.

Chromosomal copy number alterations and chromosomal rearrangements are frequent mutations in human cancer. Unlike copy number alterations, little is known about the role and occurrence of chromosomal rearrangements in breast cancer. This may be due to the fact that chromosome-based breakpoint analysis is widely restricted to cultured cells.

Accumulation of DSBs in gamma-H2AX domains fuel chromosomal aberrations.

DNA double strand breaks (DSBs) pose a severe hazard to the genome as erroneous rejoining of DSBs can lead to mutation and cancer. Here, we have investigated the correlation between X irradiation-induced gamma-H2AX foci, theoretically induced DSBs, and the minimal number of mis-rejoined DNA breaks (MNB) in irradiated lymphocytes obtained from two healthy humans by painting of the whole chromosome complement by spectral karyotyping. There were less gamma-H2AX foci/dose than theoretically expected, while misrepair, as expressed by MNB/gamma-H2AX focus, was similar at 0.

RET rearrangements in post-Chernobyl papillary thyroid carcinomas with a short latency analysed by interphase FISH.

Tissue samples from 13 post-Chernobyl childhood thyroid tumours that occurred within a short period of time (4-8 years) after the Chernobyl accident have been investigated by interphase FISH analysis for rearrangements of RET. In all, 77% of cases showed RET/PTC rearrangements and a distinct intratumoural genetic heterogeneity. The data were compared to findings on 32 post-Chernobyl PTCs that occurred after a longer period of time (9-12 years) after the accident.

Chromosomal imbalances in post-chernobyl thyroid tumors.

Tissue samples from 60 post-Chernobyl childhood thyroid tumors have been investigated. We used comparative genomic hybridization (CGH) to detect chromosomal gains and losses within the tumor DNA. This is the first CGH study on childhood thyroid tumors.

Gene amplification of atypical PKC-binding PARD3 in radiation-transformed neoplastic retinal pigment epithelial cell lines.

Neoplastic transformation induced by ionizing radiation was studied using a human retinal pigment epithelial cell line immortalized by telomerase. Radiation-transformed cell clones were tumorigenic in athymic mice and were analyzed by G-banding and comparative genomic hybridization (CGH). Radiation-transformed cloned cell lines and cell lines derived from tumors produced in athymic nude mice following transplantation exhibited a recurrent karyotype:45,XX,der(10),-13.

Differential mutation frequency in mitochondrial DNA from thyroid tumours.

Lack of a chromatin structure and histone protection makes mitochondrial DNA susceptible to oxidative damage. Suboptimal DNA repair leads to a higher frequency of mitochondrial mutations, which are associated with aging, carcinogenesis and environmental insult. The instability of the hypervariable region II of the mitochondrial genome was investigated in radiation-associated thyroid tumours, which were diagnosed in children from Belarus after the accident at the Chernobyl nuclear power plant, and from 40 sporadic thyroid tumours from Munich.

Instability of microsatellites in radiation-associated thyroid tumours with short latency periods.

Purpose: To determine the instability of microsatellite sequences in post-Chernobyl thyroid tumours from children and young adults, and to ascertain whether they correlated with the age of the patient at the time of the accident and the tumour latency period.

Materials And Methods: The stability of 26 microsatellite markers was investigated in 122 radiation-associated thyroid tumours (96 children, 26 adults) from Belarus and 39 spontaneous thyroid tumours (adults) from Munich without radiation history.

Results: A significant correlation between patient age at the time of the accident and the instability of microsatellite sequences was established.

Clonal chromosomal aberrations in simian virus 40-transfected human thyroid cells and in derived tumors developed after in vitro irradiation.

In vitro model cell systems are important tools for studying mechanisms of radiation-induced neoplastic transformation of human epithelial cells. In our study, the human thyroid epithelial cell line HTori-3 was analyzed cytogenetically following exposure to different doses of alpha- and gamma-irradiation and subsequent tumor formation in athymic nude mice. Combining results from G-banding, comparative genomic hybridization, and spectral karyotyping, chromosome abnormalities could be depicted in the parental line HTori-3 and in nine different HTori lines established from the developed tumors.

Neoplastic transformation and cytogenetic changes after Gamma irradiation of human epithelial cells expressing telomerase.

Neoplastic transformation of human epithelial cells by radiation has previously been investigated using cell lines immortalized with viral vectors. There are disadvantages to this approach, and we report here the results of studies using a human retinal pigment epithelial cell line (340RPE-T53) immortalized by treatment with telomerase. After exposure of the cells to fractionated doses of gamma radiation, there was a marked increase in anchorage-independent growth of the surviving cells.

Microsatellite instability and loss of heterozygosity in radiation-associated thyroid carcinomas of Belarussian children and adults.

DNA from 129 paired thyroid tumorous and non-tumorous tissue samples of Belarussian children (102 patients; age at surgery View Article and Find Full Text PDF

Distinct frequency of ret rearrangements in papillary thyroid carcinomas of children and adults from Belarus.

Rearrangements of the ret oncogene were investigated in papillary thyroid carcinomas (PTC) from 51 Belarussian children with a mean age of 3 years at the time of the Chernobyl radiation accident. For comparison, 16 PTC from exposed Belarussian adults and 16 PTC from German patients without radiation history were included in the study. ret rearrangements were detected and specified by RT-PCR and direct sequencing using specific primers for ret/PTC1, 2 and 3.

Cytogenetic changes in radiation-induced tumors of the thyroid.

Thyroid carcinoma incidence is increased significantly after ionizing irradiation; however, the possible mechanisms have not yet been identified. To provide clues for an understanding of the radiation-induced transformation of thyroid epithelium, we analyzed the karyotypes of 56 childhood thyroid tumors that appeared in Belarus after the Chernobyl nuclear accident in 1986. We also studied eight secondary thyroid tumors that developed after radiotherapy.