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Search Results: 1 - 10 of 1811 matches for " Gabriele Schackert "
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SOX2-RNAi attenuates S-phase entry and induces RhoA-dependent switch to protease-independent amoeboid migration in human glioma cells
Felix Oppel, Nadja Müller, Gabriele Schackert, Sandy Hendruschk, Daniel Martin, Kathrin D Geiger, Achim Temme
Molecular Cancer , 2011, DOI: 10.1186/1476-4598-10-137
Abstract: Retroviral shRNA-vectors were utilized to stably knockdown SOX2 in U343-MG and U373-MG cells. The resulting phenotype was investigated by Western blot, migration/invasion assays, RhoA G-LISA, time lapse video imaging, and orthotopic xenograft experiments.SOX2 depletion results in pleiotropic effects including attenuated cell proliferation caused by decreased levels of cyclinD1. Also an increased TCF/LEF-signaling and concomitant decrease in Oct4 and Nestin expression was noted. Furthermore, down-regulation of focal adhesion kinase (FAK) signaling and of downstream proteins such as HEF1/NEDD9, matrix metalloproteinases pro-MMP-1 and -2 impaired invasive proteolysis-dependent migration. Yet, cells with knockdown of SOX2 switched to a RhoA-dependent amoeboid-like migration mode which could be blocked by the ROCK inhibitor Y27632 downstream of RhoA-signaling. Orthotopic xenograft experiments revealed a higher tumorigenicity of U343-MG glioma cells transduced with shRNA targeting SOX2 which was characterized by increased dissemination of glioma cells.Our findings suggest that SOX2 plays a role in the maintenance of a less differentiated glioma cell phenotype. In addition, the results indicate a critical role of SOX2 in adhesion and migration of malignant gliomas.Despite multimodal treatment the prognosis for glioblastoma (GBM), the most common and most malignant brain tumor remains poor, with the majority of patients dying within 1 year after diagnosis [1]. Glioblastomas, gliomas of WHO grade IV, diffusely spread into the surrounding brain and the invading tumor cells migrate along the white matter tracks and assemble satellites around neuron cell bodies, blood vessels and the subpial region [2,3]. Since glioblastoma cells infiltrate wide areas of the brain every resection of the bulk tumor is usually followed by a tumor re-initiation at the resection site or at another place in the brain [4,5]. The cellular origin of glioblastoma is still under investigation and it is h
An Extremely Rare, Remote Intracerebral Metastasis of Oral Cavity Cancer: A Case Report
Mario Leimert,Tareq A. Juratli,Claudia Lindner,Kathrin D. Geiger,Johannes Gerber,Gabriele Schackert,Matthias Kirsch
Case Reports in Medicine , 2013, DOI: 10.1155/2013/257046
Abstract: Distant brain metastases from oral squamous cell carcinomas (OSCC) are extremely rare. Here we describe a case of a 53-year-old man with a primary OSCC who referred to the neurosurgical department because of epileptic seizures. MR imaging revealed an enhancing lesion in the right parietal lobe. A craniotomy with tumor removing was performed. Histopathological examination verified an invasive, minimally differentiated metastasis of the primary OSCC. The patient refused whole brain radiation therapy and died from pulmonary metastatic disease 10 months after the neurosurgical intervention without any cerebral recurrence. To the authors’ knowledge, only two similar cases have been previously reported. 1. Introduction Remote brain metastases from oral squamous cell carcinomas (OSCC) are an extremely rare occurrence. To date, only few cases have been reported previously [1, 2]. In contrast, direct intracranial invasion is not infrequent in patients with nasopharyngeal carcinoma (NPC) at a locally advanced stage [3]. Incidence of brain metastases following NPC may be increasing secondary to advancements in the treatment of systemic disease and earlier detection by more sensitive imaging modalities [4]. Most distant metastases from squamous cell carcinoma (SCC) are reported to occur in the liver, lungs, and bones [5]. Therefore, preoperative tumor staging is focussed on these sites (CT scan of the chest, radionuclide bone scans, and ultrasound of the liver). In the following case study, we present a patient who developed a histologically confirmed brain metastasis of OSCC. The patient developed symptoms from his cerebral metastasis 29 months after the primary disease was diagnosed. 2. Case Description A 53-year-old man with a 29-month history of a slowly enlarging ulcer on the bottom of the right lateral oral cavity was referred to our Department of Head and Neck surgery. After biopsy, a radical surgical resection of the tumor with supraomohyoid and functional neck dissection in continuity and reconstruction with a radial forearm free flap was performed. Histopathological work-up diagnosed a primary oral squamous cell carcinoma stage T3N3 (Figure 3(a)). Based on the stage of this diagnosis, adjuvant radiotherapy was initiated with a total dose of 64?Gy delivered in 32 fractions to both sides of the neck and the primary site. A CT scan revealed bilateral small pulmonary nodules, which were diagnosed as pulmonary metastases, but the patient declined chemotherapy. After radiation therapy, he was well and with stable disease for 26 months. Then, after a 3-week
Atypical Central Neurocytoma with Recurrent Spinal Dissemination over a Period of 20 Years: A Case Report and Review of the Literature
Tareq A. Juratli,Kathrin Geiger,Mario Leimert,Gabriele Schackert,Matthias Kirsch
Case Reports in Neurological Medicine , 2013, DOI: 10.1155/2013/925647
Abstract: We present an unusual case of a late recurrent central neurocytoma that was rediagnosed as an ependymoma and neurocytoma in accordance with changes in histological classifications. Case Description. A 56-year-old male teacher presented with incomplete transverse syndrome due to several intradural extramedullary tumors at the level of lumbar vertebrae 1–3. The histological diagnosis at the time was atypical ependymoma. One year later, two additional tumors were removed at the L5-S1 vertebral level. For 12 years, the patient remained tumor free on followup. Fourteen years after the initial diagnosis, the patient presented with thoracic paresthesias due to two new extramedullary tumors in the C7-T1 and the T8-T9 vertebral levels. After complete removal of the tumors, a radiological survey revealed an intracranial lesion in the third ventricle. Five months later, an additional lesion recurrence was removed surgically. The most recent histological diagnosis revealed an atypical central neurocytoma. In retrospect, the previous tumors were reclassified as neurocytoma according to the additional immunohistochemistry evidence. Discussion. There is no standard adjuvant treatment regimen for atypical neurocytoma; therefore, the patient is currently under close followup. Modern histopathological diagnosis is essential in these cases. Potential routes for dissemination of the tumor should be considered upon first recurrence. 1. Introduction Central neurocytomas are rare benign tumors of the central nervous system, characterized by their intraventricular localization. They are considered to arise from precursor cells of the septum pellucidum. They predominantly occur in young adults and generally have a favorable outcome, although cases with an aggressive clinical course and recurrences have been described. Historically, many of these lesions were regarded as either intraventricular oligodendroglioma or as ependymoma until detailed immunohistological clarification of their neuronal phenotypes was established. Neurocytoma was first described by Hassoun et al. [1] and is now a well-established diagnosis included in the latest WHO Classification [2]. In the literature, only a few neurocytomas were reported with an extraventricular location, including cerebral hemispheres [3], thalamus [4], cerebellum [5], pons [6], amygdala [7], retina [8], and in some rare cases the spinal cord [9]. Herein, we report a case of an atypical central neurocytoma with recurrent spinal dissemination over a period of 20 years. 2. Case Report A 56-year-old Caucasian male teacher was first seen
Tumor Evasion from T Cell Surveillance
Katrin T pfer,Stefanie Kempe,Nadja Müller,Marc Schmitz,Michael Bachmann,Marc Cartellieri,Gabriele Schackert,Achim Temme
Journal of Biomedicine and Biotechnology , 2011, DOI: 10.1155/2011/918471
Abstract: An intact immune system is essential to prevent the development and progression of neoplastic cells in a process termed immune surveillance. During this process the innate and the adaptive immune systems closely cooperate and especially T cells play an important role to detect and eliminate tumor cells. Due to the mechanism of central tolerance the frequency of T cells displaying appropriate arranged tumor-peptide-specific-T-cell receptors is very low and their activation by professional antigen-presenting cells, such as dendritic cells, is frequently hampered by insufficient costimulation resulting in peripheral tolerance. In addition, inhibitory immune circuits can impair an efficient antitumoral response of reactive T cells. It also has been demonstrated that large tumor burden can promote a state of immunosuppression that in turn can facilitate neoplastic progression. Moreover, tumor cells, which mostly are genetically instable, can gain rescue mechanisms which further impair immune surveillance by T cells. Herein, we summarize the data on how tumor cells evade T-cell immune surveillance with the focus on solid tumors and describe approaches to improve anticancer capacity of T cells.
Novel CIC Point Mutations and an Exon-Spanning, Homozygous Deletion Identified in Oligodendroglial Tumors by a Comprehensive Genomic Approach Including Transcriptome Sequencing
Sophie Eisenreich, Khalil Abou-El-Ardat, Karol Szafranski, Jaime A. Campos Valenzuela, Andreas Rump, Janice M. Nigro, Rolf Bjerkvig, Eva-Maria Gerlach, Karl Hackmann, Evelin Schr?ck, Dietmar Krex, Lars Kaderali, Gabriele Schackert, Matthias Platzer, Barbara Klink
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0076623
Abstract: Oligodendroglial tumors form a distinct subgroup of gliomas, characterized by a better response to treatment and prolonged overall survival. Most oligodendrogliomas and also some oligoastrocytomas are characterized by a unique and typical unbalanced translocation, der(1,19), resulting in a 1p/19q co-deletion. Candidate tumor suppressor genes targeted by these losses, CIC on 19q13.2 and FUBP1 on 1p31.1, were only recently discovered. We analyzed 17 oligodendrogliomas and oligoastrocytomas by applying a comprehensive approach consisting of RNA expression analysis, DNA sequencing of CIC, FUBP1, IDH1/2, and array CGH. We confirmed three different genetic subtypes in our samples: i) the “oligodendroglial” subtype with 1p/19q co-deletion in twelve out of 17 tumors; ii) the “astrocytic” subtype in three tumors; iii) the “other” subtype in two tumors. All twelve tumors with the 1p/19q co-deletion carried the most common IDH1 R132H mutation. In seven of these tumors, we found protein-disrupting point mutations in the remaining allele of CIC, four of which are novel. One of these tumors also had a deleterious mutation in FUBP1. Only by integrating RNA expression and array CGH data, were we able to discover an exon-spanning homozygous microdeletion within the remaining allele of CIC in an additional tumor with 1p/19q co-deletion. Therefore we propose that the mutation rate might be underestimated when looking at sequence variants alone. In conclusion, the high frequency and the spectrum of CIC mutations in our 1p/19q-codeleted tumor cohort support the hypothesis that CIC acts as a tumor suppressor in these tumors, whereas FUBP1 might play only a minor role.
A Sieve for Prime Based on Extension Form of Not Prime  [PDF]
Gabriele Martino
American Journal of Computational Mathematics (AJCM) , 2013, DOI: 10.4236/ajcm.2013.31014
Abstract:

This paper will illustrate two versions of an algorithm for finding prime number up to N, which give the first version complexity

\"\" (1)

where c1, c2 are constants, and N is the input dimension, and gives a better result for the second version. The method is based on an equation that expresses the behavior of not prime numbers. With this equation it is possible to construct a fast iteration to verify if the not prime number is generated by a prime and with which parameters. The second method differs because it does not pass other times over a number that has been previously evaluated as not prime. This is possible for a recurrence of not prime number that is (mod 3) = 0. The complexity in this case is better than the first. The comparison is made most with Mathematics than by computer calculation as the number N should be very big to appreciate the difference between the two versions. Anyway the second version results better. The algorithms have been

Primality Test  [PDF]
Gabriele Martino
American Journal of Computational Mathematics (AJCM) , 2013, DOI: 10.4236/ajcm.2013.31009
Abstract:

In this paper we will give an algorithm that in the worst case solve the question about the primality of a number in \"\" but that gives better result if the number is not prime (constant operation). Firstly, we will introduce an equation on which are based not prime numbers. With this equation it is possible to deduce the prime number that generates a not prime number and to establish an equation in which if exists a certain integer the number is not prime and therefore vice versa to deduce if it is prime.

Solving a Traveling Salesman Problem with a Flower Structure  [PDF]
Gabriele Martino
Journal of Applied Mathematics and Physics (JAMP) , 2014, DOI: 10.4236/jamp.2014.27079
Abstract:

This works aims to give an answer to the problem P = NP? The result is positive with the criteria that solve the Traveling Salesman Problem in polynomial cost of the input size and a proof is given. This problem gets a solution because a polyhedron, with a cut flower looking, is introduced instead of graph (e.g. tree).

Die Behandlung von lteren Patienten mit benignen oder malignen Hirntumoren
Krex D,Rudolph K,Schackert G
Journal für Neurologie, Neurochirurgie und Psychiatrie , 2011,
Abstract: Der demographische Wandel spiegelt sich zunehmend in unserem klinischen Alltag wider. Der Anteil an alten Patienten wird auch in der Neurochirurgie stetig gr er. Menschen jenseits des 65. Lebensjahres wurden bisher nur vereinzelt in klinischen Studien berücksichtigt, sodass die Datenlage zu evidenzbasierten Therapieempfehlungen dieser Altersgruppe entsprechend dürftig ist. Die vorliegende retrospektive Analyse besch ftigt sich mit der Frage, ob bei Patienten jenseits des 75. Lebensjahres mit einem Glioblastom oder einem Meningeom generell die gleiche operative und adjuvante Therapie angewendet werden sollte wie bei jüngeren Patienten, und ob h ufiger oder schwerwiegendere Komplikationen in dieser Altersgruppe auftreten. 105 Patienten mit Glioblastomen oder Meningeomen 75 Jahre wurden 97 Patienten mit gleichen Diagnosen und einem Alter 50 Jahre gegenübergestellt. Der Allgemein- und neurologische Zustand war bei den lteren initial schlechter als bei den Jüngeren. Die OP-assoziierten Komplikationen waren in beiden Gruppen gleich verteilt. Auff llig war jedoch ein erh hter Anteil an Patienten mit Antriebs- und Hirnleistungsst rungen in der Gruppe der 75-J hrigen, was zu einer vorübergehenden Pflegebedürftigkeit führte. Maligne Gliome wurden bei den lteren deutlich weniger adjuvant behandelt und das überleben war in dieser Gruppe signifikant schlechter. Daraus resultiert, dass auch alte Patienten mit malignen Gliomen oder Meningeomen in gleichem Ma e neurochirurgisch behandelt werden sollten wie jüngere Patienten. Auch sollte über eine intensivere adjuvante Therapie nachgedacht werden, um das überleben zu verbessern, was aber letztlich in klinischen Studien beurteilt werden muss, die auch diese Altersgruppe berücksichtigen.
On the Fractal Design in Human Brain and Nervous Tissue  [PDF]
Gabriele A. Losa
Applied Mathematics (AM) , 2014, DOI: 10.4236/am.2014.512165
Abstract:


Digital imaging techniques have enabled to gain insight into complex structure-functional processes involved in the neo-cortex maturation and in brain development, already recognized in anatomical and histological preparations. Despite such a refined technical progress most diagnostic records sound still elusive and unreliable because of use of conventional morphometric approaches based on a unique scale of measure, inadequate for investigating irregular cellular components and structures which shape nervous and brain tissues. Instead, these could be efficiently analyzed by adopting principles and methodologies derived from the Fractal Geometry. Through his masterpiece, The Fractal Geometry of Nature [1], Benoît Mandelbrot has provided a novel epistemological framework for interpreting the real life and the natural world as they are, preventing whatever approximation or subjective sight. Founded upon a body of well-defined laws and coherent principles, the Fractal Geometry is a powerful tool for recognizing and quantitatively describing a good many kinds of complex shapes, living forms, organized patterns, and morphologic features long range correlated with a broad network of functional interactions and metabolic processes that contribute to building up adaptive responses making life sustainable. Scale free dynamics characterized biological systems which develop through the iteration of single generators on different scales thus preserving proper self-similar traits. In the last decades several studies have contributed to showing how relevant may be the recognition of fractal properties for a better understanding of brain and nervous tissues either in healthy conditions or in altered and pathological states.


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