Search

Your search keyword '"Knittel, G."' showing total 181 results
Start Over Author "Knittel, G."
181 results on '"Knittel, G."'

1. Deregulation and epigenetic modification of BCL2-family genes cause resistance to venetoclax in hematologic malignancies

Author

Thomalla, D., Beckmann, L., Grimm, C., Oliverio, M., Meder, L., Herling, C.D., Nieper, P., Feldmann, T., Merkel, O., Lorsy, E., da Palma Guerreiro, A., von Jan, J., Kisis, I., Wasserburger, E., Claasen, J., Faitschuk-Meyer, E., Altmüller, J., Nürnberg, P., Yang, T.-P., Lienhard, M., Herwig, R., Kreuzer, K.-A., Pallasch, C.P., Büttner, R., Schäfer, S.C., Hartley, J., Abken, H., Peifer, M., Kashkar, H., Knittel, G., Eichhorst, B., Ullrich, R.T., Herling, M., Reinhardt, H.C., Hallek, M., Schweiger, M.R., and Frenzel, L.P.

Published
2022
Full Text
View/download PDF

8. V184: Restoration of Atm induces lymphoma regression in vivo andis mediated by cell autonomous and non-cell autonomousmechanisms

Author

Riabinska, A., Schmitt, A., Merseburg, Andrea, Persigehl, T., Wunderlich, T., Büttner, R., Reinhardt, H, Fritz, C., Knittel, G., Torgovnick, A., Heneweer, C., Wittersheim, M., Frenzel, L., Wunderlich, C., and Jachimowicz, R

Subjects
ddc:350
Abstract

Addiction of different cancers to particular genetic lesions can be frequently used for development of sophisticated targeting strategies. In parallel tosuccess of oncogene inhibition, restoration of mutant tumor suppressors,such as TP53, has been shown to induce tumor regression in many murinemodels. On contrary, re-expression of BRCA2 supported chemotherapyresistance and continued proliferation of cancer cells. Ataxia Telangiectasia Mutated (ATM) kinase plays a key role in DNA-damage responsesingling and therefore, protects genome stability. ATM is a potent tumorsuppressor, frequently inactivated or downregulated in a wide range ofhuman cancers. Germline mutations in ATM cause Ataxia-telangiectasia, which is characterized by cerebellar ataxia and cancer predisposition.Here, we aim to understand whether loss of functional ATM kinase, whichacts upstream of both: p53 and BRCA2, is critical for tumor maintenance.To address this question, we generated a reactivatable murine Atm knockout allele, which phenocopies described Atm knockout lines. Reactivationof ATM in thymic T-cell lymphomas and Myc-driven Non-Hodgkin´sB-cell lymphomas led to tumor regression, reduced proliferation and induction of apoptosis in the tumor tissue.Furthermore transplantation experiments, in which we could distinguishbetween Atm re-expression in tumor cells and stroma, revealed importantrole of ATM in the tumor microenvironment.Our results demonstrate that continued lack of Atm expression is criticalfor the maintenance of the oncogenic state in B- and T cell lymphomasin vivo. In addition, our data indicate, that transplantation of ATM-proficient immune cells might be considered as a therapeutic approach fortreatment of cancer in A-T patients

Published
2017

9. Differential ibrutinib sensitivity in Cd79b‐mutant and wildtype subtypes of a novel Myd88‐driven DLBCL mouse model.

Author

Flümann, R., Hansen, J., Klein, S., Goldfarb‐Wittkopf, H., Pfeiffer, P., Wirtz, J., Lütz, A. F., Persigehl, T., Büttner, R., Jachimowicz, R., Knittel, G., and Reinhardt, H. C.

Subjects
DIFFUSE large B-cell lymphomas, LABORATORY mice, ANIMAL disease models, B cell receptors, B cell differentiation
Abstract

B Conclusions: b Taken together, we refined existing I Myd88 i p.L252p and I BCL2 i -driven MCD/C5 DLBCL mouse models by co-expressing the I Cd79b i p.Y195H mutation. B Methods: b We generated an allele that allows the conditional expression of I Cd79b i p.Y195H (the murine orthologue of I CD79B i p.Y196H) from the endogenous locus and bred it to our established DLBCL mouse models. I Cd79b i -mutant murine lymphomas exhibited increased BCR activation levels, resulting in an increased sensitivity towards BTK inhibition, when compared to I Cd79b i wt control tumors. [Extracted from the article]

Published
2023
Full Text
View/download PDF

10. Targeting transcription-coupled nucleotide excision repair overcomes resistance in chronic lymphocytic leukemia

Author

Lohmann, G., Vasyutina, E., Bloehdorn, J., Reinart, N., Schneider, J. I., Babu, V., Knittel, G., Crispatzu, G., Mayer, P., Prinz, C., Muenzner, J. K., Biersack, B., Efremov, D. G., Chessa, L., Herling, C. D., Stilgenbauer, S., Hallek, M., Schobert, R., Reinhardt, H. C., Schumacher, B., Herling, M., Lohmann, G., Vasyutina, E., Bloehdorn, J., Reinart, N., Schneider, J. I., Babu, V., Knittel, G., Crispatzu, G., Mayer, P., Prinz, C., Muenzner, J. K., Biersack, B., Efremov, D. G., Chessa, L., Herling, C. D., Stilgenbauer, S., Hallek, M., Schobert, R., Reinhardt, H. C., Schumacher, B., and Herling, M.

Abstract

Treatment resistance becomes a challenge at some point in the course of most patients with chronic lymphocytic leukemia (CLL). This applies to fludarabine-based regimens, and is also an increasing concern in the era of more targeted therapies. As cells with low-replicative activity rely on repair that triggers checkpoint-independent noncanonical pathways, we reasoned that targeting the nucleotide excision repair (NER) reaction addresses a vulnerability of CLL and might even synergize with fludarabine, which blocks the NER gap-filling step. We interrogated here especially the replication-independent transcription-coupled-NER ((TC)-NER) in prospective trial patients, primary CLL cultures, cell lines and mice. We screen selected (TC)-NER-targeting compounds as experimental (illudins) or clinically approved (trabectedin) drugs. They inflict transcription-stalling DNA lesions requiring TC-NER either for their removal (illudins) or for generation of lethal strand breaks (trabectedin). Genetically defined systems of NER deficiency confirmed their specificity. They selectively and efficiently induced cell death in CLL, irrespective of high-risk cytogenetics, IGHV status or clinical treatment history, including resistance. The substances induced ATM/p53-independent apoptosis and showed marked synergisms with fludarabine. Trabectedin additionally perturbed stromal-cell protection and showed encouraging antileukemic profiles even in aggressive and transforming murine CLL. This proof-of-principle study established (TC)-NER as a mechanism to be further exploited to resensitize CLL cells.

Published
2017

11. Novel models of high-risk CLL reveal an actionable PARP1 dependence in ATM-defective CLL in vivo

Author

Knittel, G., Korovkina, D., Liedgens, P., Rehkaemper, T., Fritz, C., Torgovnick, A., Al-Baldawi, Y., Al-Maarri, M., Cun, Y., Fedorchenko, O., Riabinska, A., Beleggia, F., Nguyen, P. -H., Wunderlich, F. T., Ortmann, M., Montesinos-Rongen, M., Tausch, E., Stilgenbauer, S., Frenzel, L., Herling, M., Herling, C., Bahlo, J., Hallek, M., Peifer, M., Buettner, R., Persigehl, T., Reinhardt, H. C., Knittel, G., Korovkina, D., Liedgens, P., Rehkaemper, T., Fritz, C., Torgovnick, A., Al-Baldawi, Y., Al-Maarri, M., Cun, Y., Fedorchenko, O., Riabinska, A., Beleggia, F., Nguyen, P. -H., Wunderlich, F. T., Ortmann, M., Montesinos-Rongen, M., Tausch, E., Stilgenbauer, S., Frenzel, L., Herling, M., Herling, C., Bahlo, J., Hallek, M., Peifer, M., Buettner, R., Persigehl, T., and Reinhardt, H. C.

Published
2017

13. Restoration of Atm induces lymphoma regression in vivo and is mediated by cell autonomous and non-cell autonomous mechanisms

Author

Riabinska, A., Schmitt, A., Fritz, C., Knittel, G., Torgovnick, A., Heneweer, C., Wittersheim, M., Frenzel, L., Wunderlich, C., Jachimowicz, R., Merseburg, A., Persigehl, T., Wunderlich, T., Buettner, R., Reinhardt, H. C., Riabinska, A., Schmitt, A., Fritz, C., Knittel, G., Torgovnick, A., Heneweer, C., Wittersheim, M., Frenzel, L., Wunderlich, C., Jachimowicz, R., Merseburg, A., Persigehl, T., Wunderlich, T., Buettner, R., and Reinhardt, H. C.

Published
2017

15. Deregulation and epigenetic modification of BCL2-family genes cause resistance to venetoclax in hematologic malignancies

Author

Thomalla, D., Beckmann, L., Grimm, C., Oliverio, M., Meder, L., Herling, C.D., Nieper, P., Feldmann, T., Merkel, O., Lorsy, E., da Palma Guerreiro, A., von Jan, J., Kisis, I., Wasserburger, E., Claasen, J., Faitschuk-Meyer, E., Altmüller, J., Nürnberg, P., Yang, T.-P., Lienhard, M., Herwig, R., Kreuzer, K.-A., Pallasch, C.P., Büttner, R., Schäfer, S.C., Hartley, J., Abken, H., Peifer, M., Kashkar, H., Knittel, G., Eichhorst, B., Ullrich, R.T., Herling, M., Reinhardt, H.C., Hallek, M., Schweiger, M.R., and Frenzel, L.P.

Abstract

The BCL2 inhibitor venetoclax has been approved to treat different hematological malignancies. Since there is no common genetic alteration causing resistance to venetoclax in CLL and B cell lymphoma, we asked if epigenetic events might be involved in venetoclax resistance. Therefore, we employed whole exome sequencing, methylated DNA immunoprecipitation sequencing and genome wide CRISPR/Cas9 screening to investigate venetoclax resistance in aggressive lymphoma and high-risk CLL patients. We identified a regulatory CpG island within the PUMApromoter which is methylated upon venetoclax treatment, mediating PUMAdownregulation on transcript and protein level. PUMAexpression and sensitivity towards venetoclax can be restored by inhibition of methyltransferases. We can demonstrate that loss of PUMA results in metabolic reprogramming with higher OXPHOS and ATP production, resembling the metabolic phenotype that is seen upon venetoclax resistance. While PUMA loss is specific for acquired venetoclax resistance but not for acquired MCL1 resistance and is not seen in CLL patients after chemotherapy-resistance, BAX is essential for sensitivity towards both venetoclax and MCL1 inhibition. As we found loss of BAX in Richter’s syndrome patients after venetoclax failure, we defined BAX-mediated apoptosis to be critical for drug resistance but not for disease progression of CLL into aggressive DLBCL in vivo. A compound screen revealed TRAIL-mediated apoptosis as a target to overcome BAX deficiency. Furthermore, antibody or CAR T cells eliminated venetoclax resistant lymphoma cells, paving a clinically applicable way to overcome venetoclax resistance.

Published
2024
Full Text
View/download PDF

16. ESTABLISHMENT OF A PRE-CLINICAL IN VIVO PLATFORM SPANNING LOW-RISK TO HIGH-RISK CLL

Author

Knittel, G., Korovkina, D., Liedgens, P., Fritz, C., Al-Baldawi, Y., Bahlo, J., Herling, C., Eichhorst, B., Hallek, M., Persigehl, T., Buettner, R., Reinhardt, H. C., Knittel, G., Korovkina, D., Liedgens, P., Fritz, C., Al-Baldawi, Y., Bahlo, J., Herling, C., Eichhorst, B., Hallek, M., Persigehl, T., Buettner, R., and Reinhardt, H. C.

Published
2016

17. B CELL-SPECIFIC CONDITIONAL EXPRESSION OF MYD88P.L252P LEADS TO THE DEVELOPMENT OF DIFFUSE LARGE B CELL LYMPHOMA IN MICE

Author

Knittel, G., Liedgens, P., Korovkina, D., Seeger, J. M., Al-Baldawi, Y., Vlantis, K., Fritz, C., Schaefer, S. C., Klatt, A., Scheel, A., Al-Maarri, M., Bezhanova, S., Montesinos-Rongen, M., Wolz, O. O., Reimann, M., Lohneis, P., Weber, A. N., Wunderlich, F. T., Pasparakis, M., Buettner, R., Persigehl, T., Schmitt, C. A., Odenthal, M., Frenzel, L. P., Kashkar, H., Reinhardt, H. C., Knittel, G., Liedgens, P., Korovkina, D., Seeger, J. M., Al-Baldawi, Y., Vlantis, K., Fritz, C., Schaefer, S. C., Klatt, A., Scheel, A., Al-Maarri, M., Bezhanova, S., Montesinos-Rongen, M., Wolz, O. O., Reimann, M., Lohneis, P., Weber, A. N., Wunderlich, F. T., Pasparakis, M., Buettner, R., Persigehl, T., Schmitt, C. A., Odenthal, M., Frenzel, L. P., Kashkar, H., and Reinhardt, H. C.

Published
2016

18. B cell-specific conditional expression of Myd88 p.L252P leads to the development of diffuse large B cell lymphoma in mice

Author

Knittel, G., Liedgens, P., Korovkina, D., Seeger, J. M., Al-Baldawi, Y., Al-Maarri, M., Fritz, C., Vlantis, K., Bezhanova, S., Scheel, A. H., Wolz, O. -O., Reimann, M., Moeller, P., Lopez, C., Staudt, L. M., Ortmann, M., Pasparakis, M., Siebert, R., Schmitt, C. A., Klatt, A. R., Wunderlich, F. T., Schaefer, S. C., Persigehl, T., Montesinos-Rongen, M., Odenthal, M., Buettner, R., Frenzel, L. P., Kashkar, H., Reinhardt, H. C., Knittel, G., Liedgens, P., Korovkina, D., Seeger, J. M., Al-Baldawi, Y., Al-Maarri, M., Fritz, C., Vlantis, K., Bezhanova, S., Scheel, A. H., Wolz, O. -O., Reimann, M., Moeller, P., Lopez, C., Staudt, L. M., Ortmann, M., Pasparakis, M., Siebert, R., Schmitt, C. A., Klatt, A. R., Wunderlich, F. T., Schaefer, S. C., Persigehl, T., Montesinos-Rongen, M., Odenthal, M., Buettner, R., Frenzel, L. P., Kashkar, H., and Reinhardt, H. C.

Published
2016

19. Targeting transcription-coupled nucleotide excision repair overcomes resistance in chronic lymphocytic leukemia

Author

Lohmann, G, primary, Vasyutina, E, additional, Bloehdorn, J, additional, Reinart, N, additional, Schneider, J I, additional, Babu, V, additional, Knittel, G, additional, Crispatzu, G, additional, Mayer, P, additional, Prinz, C, additional, Muenzner, J K, additional, Biersack, B, additional, Efremov, D G, additional, Chessa, L, additional, Herling, C D, additional, Stilgenbauer, S, additional, Hallek, M, additional, Schobert, R, additional, Reinhardt, H C, additional, Schumacher, B, additional, and Herling, M, additional

Published
2016
Full Text
View/download PDF

22. Giga-voxel rendering from compressed data on a display wall

Author

Parys, R., Knittel, G., and Skala, Václav

Subjects
paralelní grafika, volume rendering, ComputingMethodologies_IMAGEPROCESSINGANDCOMPUTERVISION, distribuovaná grafika, Data_CODINGANDINFORMATIONTHEORY, programování grafických procesorů, distributed graphics, parallel graphics, GPU programming, objemové vykreslování, ComputingMethodologies_COMPUTERGRAPHICS
Abstract

We present a parallel system capable of rendering multi-gigabyte data sets on a multi-megapixel display wall at interactive rates. The system is based on Residual Vector Quantization which allows us to render extremely large data sets out of the graphics memory. At 0.75 bits per voxel, such large data sets can even be kept on a consumerlevel graphics card. As an example we compress the whole full color “Visible Human Female” data set, approximately 21GByte in size, down to 700MByte. Taking advantage of the fixed code length and the extremely simple decompression scheme of RVQ, all decompression is done on the GPU at very high rates. For each frame the data set is decompressed into small subvolumes which are rendered front to back. Classification and shading can be moved into the decompression step, speeding up the rendering pass.

Published
2009

33. GPS-Squitter Automatic Dependent Surveillance Broadcast: Flight Testing in the Gulf of Mexico

Author

MASSACHUSETTS INST OF TECH LEXINGTON LINCOLN LAB, Boisevert, R. E., Burrows, M. L., Bussolari, S. R., Knittel, G. H., Owen, M. R., MASSACHUSETTS INST OF TECH LEXINGTON LINCOLN LAB, Boisevert, R. E., Burrows, M. L., Bussolari, S. R., Knittel, G. H., and Owen, M. R.

Abstract

During November - December 1994, MIT Lincoln Laboratory conducted a field evaluation of the air surveillance capabilities of GPS-Squitter in the Gulf of Mexico. Three squitter ground stations were located in the vicinity of Morgan City, Louisiana, for this evaluation: two were located on offshore oil platforms, and the third was located at an onshore heliport. Surveillance coverage tests were flown over the Gulf with three test aircraft-two helicopters and one Cessna 421 fixed- wing aircraft. The helicopters flew at altitudes ranging from 100 to 2000 feet above sea level and the Cessna flew at 7500 and 20,000 feet. Extended squitter messages broadcast by each of the test aircraft provided aircraft position and identification. This report documents results of these tests and compares measured coverage to predicted coverage from the ground stations. Based on the good agreement between predicted and measured performance, a description of a possible operational system is included that would provide surveillance of the entire Gulf region serviced by oil platform helicopters. The report concludes that GPS- Squitter is a near-term option for providing accurate, real-time surveillance of aircraft operating in the offshore airspace in the Gulf of Mexico., Original contains color plates: All DTIC/NTIS reproductions will be in black and white.

Published
1995

Catalog

Books, media, physical & digital resources
See catalog results