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50 results on '"Reinhardt, H. C."'

1. CDK9 inhibition as an effective therapy for small cell lung cancer

Author

Valdez Capuccino, L., Kleitke, T., Szokol, B., Svajda, L., Martin, F., Bonechi, F., Krekó, M., Azami, S., Montinaro, A., Wang, Y., Nikolov, V., Kaiser, L., Bonasera, D., Saggau, J., Scholz, T., Schmitt, A., Beleggia, F., Reinhardt, H. C., George, J., Liccardi, G., Walczak, H., Tóvári, J., Brägelmann, J., Montero, J., Sos, M. L., Őrfi, L., and Peltzer, N.

Published
2024
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2. Gene expression-based outcome prediction in advanced stage classical Hodgkin lymphoma treated with BEACOPP

Author

Jachimowicz, Ron D., Klapper, Wolfram, Glehr, Gunther, Müller, Horst, Haverkamp, Heinz, Thorns, Christoph, Hansmann, Martin Leo, Möller, Peter, Stein, Harald, Rehberg, Thorsten, von Tresckow, Bastian, Reinhardt, H. C., Borchmann, Peter, Chan, Fong Chun, Spang, Rainer, Scott, David W., Engert, Andreas, Steidl, Christian, Altenbuchinger, Michael, and Rosenwald, Andreas

Published
2021
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3. ECP versus ruxolitinib in steroid-refractory chronic GVHD – a retrospective study by the EBMT transplant complications working party

Author

Penack, O., Peczynski, C., Boreland, W., Lemaitre, J., Reinhardt, H. C., Afanasyeva, K., Avenoso, D., Holderried, T. A. W., Kornblit, B. T., Gavriilaki, E., Martinez, C., Chiusolo, Patrizia, Mico, M. C., Dagunet, E., Wichert, S., Ozdogu, H., Piekarska, A., Kinsella, F., Basak, G. W., Schoemans, H., Koenecke, C., Moiseev, I., Peric, Z., Chiusolo P. (ORCID:0000-0002-1355-1587), Penack, O., Peczynski, C., Boreland, W., Lemaitre, J., Reinhardt, H. C., Afanasyeva, K., Avenoso, D., Holderried, T. A. W., Kornblit, B. T., Gavriilaki, E., Martinez, C., Chiusolo, Patrizia, Mico, M. C., Dagunet, E., Wichert, S., Ozdogu, H., Piekarska, A., Kinsella, F., Basak, G. W., Schoemans, H., Koenecke, C., Moiseev, I., Peric, Z., and Chiusolo P. (ORCID:0000-0002-1355-1587)

Abstract

Ruxolitinib has become the new standard of care for steroid-refractory and steroid-dependent chronic GVHD (SR-cGVHD). Our aim was to collect comparative data between ruxolitinib and extracorporeal photophoresis (ECP). We asked EBMT centers if they were willing to provide detailed information on GVHD grading, -therapy, -dosing, -response and complications for each included patient. 31 centers responded positively and we included all patients between 1/2017-7/2019 treated with ECP or ruxolitinib for moderate or severe SR-cGVHD. We identified 84 and 57 patients with ECP and ruxolitinib, respectively. We performed multivariate analyses adjusted on grading and type of SR-cGVHD (steroid dependent vs. refractory vs. intolerant to steroids). At day+180 after initiation of treatment for SR-cGVHD the odds ratio in the ruxolitinib group to achieve overall response vs. the ECP group was 1.35 (95% CI = [0.64; 2.91], p = 0.43). In line, we detected no statistically significant differences in overall survival, progression-free survival, non-relapse mortality and relapse incidence. The clinical significance is limited by the retrospective study design and the current data can’t replace prospective studies on ECP in SR-cGVHD. However, the present results contribute to the accumulating evidence on ECP as an effective treatment option in SR-cGVHD.

Published
2024

5. Exploring risk factors for non-response to CAR T-cell therapy in large B-cell lymphoma: A binational multicenter project on potential predictors of outcome

Author

Voltin, C., additional, Winkelmann, M., additional, Farolfi, A., additional, Beckmann, L., additional, Kobe, C., additional, Borchmann, P., additional, Fanti, S., additional, Subklewe, M., additional, Drzezga, A., additional, Kunz, W. G., additional, Herrmann, K., additional, Reinhardt, H. C., additional, Seifert, R., additional, Albring, J. C., additional, Blumenberg, V., additional, von Tresckow, B., additional, Paccagnella, A., additional, Gödel, P., additional, Flossdorf, S., additional, and Hanoun, C., additional

Published
2023
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7. Deregulation and epigenetic modification of BCL2-family genes cause resistance to venetoclax in hematologic malignancies

Author

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

Published
2022
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8. P1024: IMPACT OF TP53 IN MYELOFIBROSIS UNDERGOING STEM CELL TRANSPLANTATION

Author

Gagelmann, N., primary, Badbaran, A., additional, Panagiota, V., additional, Wolschke, C., additional, Ayuk, F., additional, Thol, F., additional, Ditschkowski, M., additional, Cassinat, B., additional, Robin, M., additional, Schroeder, T., additional, Heuser, M., additional, Reinhardt, H. C., additional, and Kröger, N., additional

Published
2022
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9. Combined inhibition of EZH2 and ATM is synthetic lethal in BRCA1-deficient breast cancer

Author

Ratz, L., Brambillasca, C., Bartke, L., Huetzen, M., Goergens, J., Leidecker, O., Jachimowicz, R., van de Ven, M., Proost, N., Siteur, B., de Korte-Grimmerink, R., Bouwman, P., Pulver, E. M., de Bruijn, R., Isensee, J., Hucho, T., Pandey, G., van Lohuizen, M., Mallmann, P., Reinhardt, H. C., Jonkers, J., Puppe, J., Ratz, L., Brambillasca, C., Bartke, L., Huetzen, M., Goergens, J., Leidecker, O., Jachimowicz, R., van de Ven, M., Proost, N., Siteur, B., de Korte-Grimmerink, R., Bouwman, P., Pulver, E. M., de Bruijn, R., Isensee, J., Hucho, T., Pandey, G., van Lohuizen, M., Mallmann, P., Reinhardt, H. C., Jonkers, J., and Puppe, J.

Published
2022

10. 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., Guerreiro, A. da Palma, von Jan, J., Kisis, I., Wasserburger, E., Claasen, J., Faitschuk-Meyer, E., Altmueller, J., Nuernberg, P., Yang, T. -P., Lienhard, M., Herwig, R., Kreuzer, K. -A., Pallasch, C. P., Buettner, R., Schaefer, 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., Frenzel, L. P., Thomalla, D., Beckmann, L., Grimm, C., Oliverio, M., Meder, L., Herling, C. D., Nieper, P., Feldmann, T., Merkel, O., Lorsy, E., Guerreiro, A. da Palma, von Jan, J., Kisis, I., Wasserburger, E., Claasen, J., Faitschuk-Meyer, E., Altmueller, J., Nuernberg, P., Yang, T. -P., Lienhard, M., Herwig, R., Kreuzer, K. -A., Pallasch, C. P., Buettner, R., Schaefer, 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. Because there is no common genetic alteration causing resistance to venetoclax in chronic lymphocytic leukemia (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 clustered regularly interspaced short palindromic repeats (CRISPR)/ CRISPR-associated protein 9 screening to investigate venetoclax resistance in aggressive lymphoma and high-risk CLL patients. We identified a regulatory CpG island within the PUMA promoter that is methylated upon venetoclax treatment, mediating PUMA downregulation on transcript and protein level. PUMA expression and sensitivity toward venetoclax can be restored by inhibition of methyltransferases. We can demonstrate that loss of PUMA results in metabolic reprogramming with higher oxidative phosphorylation and adenosine triphosphate production, resembling the metabolic phenotype that is seen upon venetoclax resistance. Although 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 toward 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 diffuse large B-cell lymphoma 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
2022

13. Prognostic factors for cellular therapies ‐ CART and allogeneic SCT ‐ in relapsed /refractory large B cell lymphoma (LBCL).

Author

Glass, B., Sureda, A., Boumendil, A., Dreger, P., Corradini, P., Ram, R., Kroeger, N., Castagna, L., Pabst, T., Kwon, M., Wulf, G., García‐Sancho, A. M., Solano, C., Stelljes, M., Reinhardt, H. C., Rubio, M. T., Malladi, R., Blaise, D., Besley, C., and Forcade, E.

Subjects
B cell lymphoma, CD19 antigen, PROGNOSIS, CELLULAR therapy
Abstract

In multivariate analysis patients with IPI (o-2) low risk at cell therapy show better OS (HR 0.81, 95% CI 0.59-1.1, I p i < 0.0001) and PFS (HR 0.62, CI: 0.46-0.83, I p i = 0.00145), comparable RI and lower NRM (HR 0.21 CI: 0.11-0.42, I p i = 0.00001) with CART compared to allo SCT. B Introduction: b Allogeneic stem cell transplantation (alloSCT) was the only curative option for younger patients (pts) with relapsed/ refractory (r/ r) LBCL (DLBCL, tFL, PMBCL). Prognostic factors for cellular therapies - CART and allogeneic SCT - in relapsed /refractory large B cell lymphoma (LBCL). [Extracted from the article]

Published
2023
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14. Serial circulating tumor DNA sequencing reveals clonal dynamics and can offer treatment guidance in relapsed/refractory diffuse large B‐cell lymphoma.

Author

Heger, J. M., Mattlener, J., Schneider, J., Schütte, D., Gödel, P., Becker, K., Kutsch, N., Balke‐Want, H., Schwarz, R. F., Reinhardt, H. C., Borchmann, P., von Tresckow, B., and Borchmann, S.

Subjects
CIRCULATING tumor DNA, DIFFUSE large B-cell lymphomas, DNA sequencing, NUCLEOTIDE sequencing
Abstract

Serial circulating tumor DNA sequencing reveals clonal dynamics and can offer treatment guidance in relapsed/refractory diffuse large B-cell lymphoma B Introduction: b Despite recent advances in the treatment of relapsed/refractory (rr)DLBCL, most patients still face progression and death. B Results: b Most patients presented with stage III/IV disease (88.4%), intermediate (58.1%) or high risk (31.4%) international prognostic index (IPI), and received CAR-T cells, high-dose chemotherapy and autologous stem cell transplantation, or other approved treatments. [Extracted from the article]

Published
2023
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18. Actionable perturbations of damage responses by TCL1/ATM and epigenetic lesions form the basis of T-PLL

Author

Schrader, A., Crispatzu, G., Oberbeck, S., Mayer, P., Putzer, S., von Jan, J., Vasyutina, E., Warner, K., Weit, N., Pflug, N., Braun, T., Andersson, E. I., Yadav, B., Riabinska, A., Maurer, B., Ferreira, M. S. Ventura, Beier, F., Altmueller, J., Lanasa, M., Herling, C. D., Haferlach, T., Stilgenbauer, S., Hopfinger, G., Peifer, M., Bruemmendorf, T. H., Nuernberg, P., Elenitoba-Johnson, K. S. J., Zha, S., Hallek, M., Moriggl, R., Reinhardt, H. C., Stern, M. -H., Mustjoki, S., Newrzela, S., Frommolt, P., Herling, M., Schrader, A., Crispatzu, G., Oberbeck, S., Mayer, P., Putzer, S., von Jan, J., Vasyutina, E., Warner, K., Weit, N., Pflug, N., Braun, T., Andersson, E. I., Yadav, B., Riabinska, A., Maurer, B., Ferreira, M. S. Ventura, Beier, F., Altmueller, J., Lanasa, M., Herling, C. D., Haferlach, T., Stilgenbauer, S., Hopfinger, G., Peifer, M., Bruemmendorf, T. H., Nuernberg, P., Elenitoba-Johnson, K. S. J., Zha, S., Hallek, M., Moriggl, R., Reinhardt, H. C., Stern, M. -H., Mustjoki, S., Newrzela, S., Frommolt, P., and Herling, M.

Abstract

T-cell prolymphocytic leukemia (T-PLL) is a rare and poor-prognostic mature T-cell malignancy. Here we integrated large-scale profiling data of alterations in gene expression, allelic copy number (CN), and nucleotide sequences in 111 well-characterized patients. Besides prominent signatures of T-cell activation and prevalent clonal variants, we also identify novel hot-spots for CN variability, fusion molecules, alternative transcripts, and progression-associated dynamics. The overall lesional spectrum of T-PLL is mainly annotated to axes of DNA damage responses, T-cell receptor/cytokine signaling, and histone modulation. We formulate a multi-dimensional model of T-PLL pathogenesis centered around a unique combination of TCL1 overexpression with damaging ATM aberrations as initiating core lesions. The effects imposed by TCL1 cooperate with compromised ATM toward a leukemogenic phenotype of impaired DNA damage processing. Dysfunctional ATM appears inefficient in alleviating elevated redox burdens and telomere attrition and in evoking a p53-dependent apoptotic response to genotoxic insults. As non-genotoxic strategies, synergistic combinations of p53 reactivators and deacetylase inhibitors reinstate such cell death execution.

Published
2018

20. Actionable perturbations of damage responses by TCL1/ATM and epigenetic lesions form the basis of T-PLL

Author

Schrader, A., primary, Crispatzu, G., additional, Oberbeck, S., additional, Mayer, P., additional, Pützer, S., additional, von Jan, J., additional, Vasyutina, E., additional, Warner, K., additional, Weit, N., additional, Pflug, N., additional, Braun, T., additional, Andersson, E. I., additional, Yadav, B., additional, Riabinska, A., additional, Maurer, B., additional, Ventura Ferreira, M. S., additional, Beier, F., additional, Altmüller, J., additional, Lanasa, M., additional, Herling, C. D., additional, Haferlach, T., additional, Stilgenbauer, S., additional, Hopfinger, G., additional, Peifer, M., additional, Brümmendorf, T. H., additional, Nürnberg, P., additional, Elenitoba-Johnson, K. S. J., additional, Zha, S., additional, Hallek, M., additional, Moriggl, R., additional, Reinhardt, H. C., additional, Stern, M.-H., additional, Mustjoki, S., additional, Newrzela, S., additional, Frommolt, P., additional, and Herling, M., additional

Published
2018
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21. 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
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22. 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

23. 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

25. 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

27. 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

28. 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

29. 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

30. 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
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31. Hypoxia-induced p38 MAPK activation reduces Mcl-1 expression and facilitates sensitivity towards BH3 mimetics in chronic lymphocytic leukemia

Author

Huelsemann, M. F., Patz, M., Beckmann, L., Brinkmann, K., Otto, T., Fandrey, J., Becker, H. J., Theurich, S., von Bergwelt-Baildon, M., Pallasch, C. P., Zahedi, R. P., Kashkar, H., Reinhardt, H. C., Hallek, M., Wendtner, C. M., Frenzel, L. P., Huelsemann, M. F., Patz, M., Beckmann, L., Brinkmann, K., Otto, T., Fandrey, J., Becker, H. J., Theurich, S., von Bergwelt-Baildon, M., Pallasch, C. P., Zahedi, R. P., Kashkar, H., Reinhardt, H. C., Hallek, M., Wendtner, C. M., and Frenzel, L. P.

Published
2015

36. Targeting monocytic‐myeloid suppressor cells through CSF1R‐blockade enhances CD19‐CAR T‐cell response in DLBCL.

Author

Gödel, P., Stahl, D., Riet, T., Flümann, R., Chmielewski, M., Blakemore, S., Segbers, P., Tetenborg, L., Reinhardt, H. C., Borchmann, P., and Ullrich, R.

Subjects
SUPPRESSOR cells, DIFFUSE large B-cell lymphomas, MYELOID differentiation factor 88, CD19 antigen, T cells, CHIMERIC antigen receptors
Abstract

To investigate CAR T cell therapy in an immunocompetent autochthonous mouse model we established murine CD19-redirected CAR-T cells that were generated using splenic T cells isolated from mice harbouring a C57BL/6N background. Targeting monocytic-myeloid suppressor cells through CSF1R-blockade enhances CD19-CAR T-cell response in DLBCL B Introduction: b Adoptive immunotherapies such as chimeric antigen receptor (CAR) T cell therapy have strongly improved the outcome of patients with diffuse large cell lymphoma (DLBCL) that are relapsed or refractory after standard chemo-immunotherapy. [Extracted from the article]

Published
2023
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37. Che-1 modulates the decision between cell cycle arrest and apoptosis by its binding to p53

Author

Desantis, A, primary, Bruno, T, additional, Catena, V, additional, De Nicola, F, additional, Goeman, F, additional, Iezzi, S, additional, Sorino, C, additional, Gentileschi, M P, additional, Germoni, S, additional, Monteleone, V, additional, Pellegrino, M, additional, Kann, M, additional, De Meo, P D, additional, Pallocca, M, additional, Höpker, K, additional, Moretti, F, additional, Mattei, E, additional, Reinhardt, H C, additional, Floridi, A, additional, Passananti, C, additional, Benzing, T, additional, Blandino, G, additional, and Fanciulli, M, additional

Published
2015
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40. Hypoxia-induced p38 MAPK activation reduces Mcl-1 expression and facilitates sensitivity towards BH3 mimetics in chronic lymphocytic leukemia

Author

Huelsemann, M F, primary, Patz, M, additional, Beckmann, L, additional, Brinkmann, K, additional, Otto, T, additional, Fandrey, J, additional, Becker, H J, additional, Theurich, S, additional, von Bergwelt-Baildon, M, additional, Pallasch, C P, additional, Zahedi, R P, additional, Kashkar, H, additional, Reinhardt, H C, additional, Hallek, M, additional, Wendtner, C M, additional, and Frenzel, L P, additional

Published
2014
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44. Expression of the Chemokine Receptor CCR10 Is Differentially Regulated in Human Podocytes in Different Glomerular Processes.

Author

Reinhardt, H. C., Zentgraf, H., Huber, T. B., Amann, K., Saleem, M. A., Liebau, M., Henger, A., Kretzler, M., Bek, M., and Pavenstädt, H.

Subjects
*IMMUNOHISTOCHEMISTRY, *WESTERN immunoblotting, *CHEMOKINES, *KIDNEY glomerulus diseases, *KIDNEY diseases
Abstract

Methods: RT-PCR, Immunohistochemistry, Western blot analysis, NADPH-Oxidase activity. Results: Chemokines and their receptors are expressed on a variety of intrinsic and infiltrating glomerular cells and play a crucial role during glomerular injury. Recently a new CC Chemokine receptor, CCR10 and its ligand CCL28 have been cloned. So far little is known about the expression and signaling of the new chemokine/ chemokine receptor pair CCL28/CCR10 in the glomerulus. Since podocyte injury is a major player in the development of glomerular injury, it was intriguing to study the expression of CCR10 and its ligand CCL28 in glomerular podocytes. We here show by RT-PCR, immunohistochemistry and Western blot analysis, that both CCR10 and CCL28 are expressed in glomerular podocytes in vivo and in vitro. We demonstrate functional expression of CCR10 in cultured human differentiated podocytes: Podocytes showed a dose dependent increase in the free cytosolic Ca++ activity after stimulation with CCL28. Moreover, CCR10 signaling results in an increased phosphorylation of ERK. This effect could be blocked by the specific MEK inhibitor PD98059. By using immunohistchemistry we show that the expression of CCR10 is upregulated in membranous nephropathy and membranoproliferative GN. A positive correlation between proteinuria and CCL28 mRNA expression was found by real time PCR studies. CCL28 stimulated podocytes showed an increased NADPH dependent generation of ROS. It has been shown, that ROS play a major role in the pathogenesis of membranous nephropathy. Conclusions: We speculate, that the chemokine/chemokine receptor pair CCL28/CCR10 may contribute to podocyte injury via an activation of the MEK/ERK pathway and an increase in ROS generation. [ABSTRACT FROM AUTHOR]

Published
2004

45. Up-Regulation of Id-1 via BMP-2 Receptors Induces Reactive Oxygen Species in Podocytes.

Author

Bek, M. J., Pache, G., Wiesemann, S., Springer, E., Liebau, M., Reinhardt, H. C., and Pavenstädt, H.

Subjects
CELL culture, WESTERN immunoblotting, CLONING, BONE morphogenetic proteins, KIDNEY diseases
Abstract

Methods: Cell culture, RT-PCR, Western blot, NADPH-oxidase acitivity, Calcium activity measurement, cloning, cDNA expression array Results: Bone morphogenetic proteins (BMPs) are secreted signaling molecules, which have been implicated to play a major role in kidney development and disease. Here we show that differentiated mouse podocytes express mRNA for BMP-2 and for the BMP receptors BMPR1A, BMPR1B, BMPRII, ACVR1A, ACVR2, and ACVR2B. BMP-2 dose-dependently increases the free cytosolic Ca2+ concentration in podocytes. cDNA expression analysis and Western blot analysis show that BMP-2 increases the expression of Id-1, a negative regulator of basic helix-loop-helix transcription factors. To investigate the role of Id-1 for podocyte function, overexpression of Id-1 was induced in mouse podocytes. Id-1 overexpressing podocytes show an increased NADPH dependent activation of ROS. This effect can be mimicked by BMP-2 in untransfected podocytes. Preincubation of podocytes with anti-Id-1-antisense oligonucleotides abolished the effect of BMP-2 on Id-1 expression and NADPH-oxidase acitivity in untransfected podocytes. Conclusions: The data indicate that BMP-2 may -- via an increased expression of Id-1 and an increased generation of ROS -- contribute to injury in podocytes. Reactive oxygen species supposedly play a major role in the pathogenesis of membranous nephropathy. [ABSTRACT FROM AUTHOR]

Published
2004

46. [Not Available].

Author

Reinhardt hc

Subjects
Female, Humans, Male, Pregnancy, Antineoplastic Agents adverse effects, Child Development, Cognition, Heart physiology, Pregnancy Complications, Neoplastic, Prenatal Exposure Delayed Effects, Radiotherapy adverse effects
Published
2016
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47. [p53-regulating pathways as targets for personalized cancer therapy].

Author

Höpker K and Reinhardt HC

Subjects
Animals, Humans, Antineoplastic Agents therapeutic use, Drug Delivery Systems methods, Models, Biological, Neoplasms drug therapy, Neoplasms metabolism, Signal Transduction drug effects, Tumor Suppressor Protein p53 metabolism
Abstract

The tumor suppressor p53 acts as a transcription factor downstream of many different stress-induced signaling pathways. Two major groups of p53-controlled genes can be distinguished. Those that mediate the initiation and maintenance of cell cycle checkpoints, and those driving apoptosis. An important determinant of the cellular reaction to DNA damage is the degree of genotoxic stress. The type of cellular response, which ranges from cell cycle arrest to apoptosis depends to a large extend on the severity of the genotoxic lesion. It remains largely unclear which molecular mechanisms govern the cellular decision between p53-driven cell cycle arrest and apoptosis. From a therapeutic perspective, this cellular decision is of utmost importance, as p53-driven apoptosis is therapeutically desired, when treating a malignant disease with DNA-damaging chemotherapy. However, a p53-driven cell cycle arrest might promote chemotherapy resistance, as it allows the tumor cells time to repair genotoxic lesions prior to the next cell division. Here, we summarize recent advances in our understanding of the molecular mechanisms controlling the functional outcome of p53 signaling. We further provide an outlook on the potential development of pharmacological interventions targeting the p53-regulating machinery to promote p53-driven apoptosis, while repressing p53-dependent cell cycle checkpoints., (© Georg Thieme Verlag KG Stuttgart · New York.)

Published
2013
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48. [Synthetic lethality as a new concept for the treatment of cancer].

Author

Herter-Sprie GS, Chen S, Höpker K, and Reinhardt HC

Subjects
Animals, Apoptosis drug effects, BRCA1 Protein genetics, BRCA2 Protein genetics, Breast Neoplasms drug therapy, Breast Neoplasms genetics, Cell Cycle drug effects, Cell Cycle genetics, Cell Division drug effects, Cell Transformation, Neoplastic drug effects, Cell Transformation, Neoplastic genetics, DNA Damage drug effects, DNA Damage genetics, DNA Mutational Analysis, DNA Repair drug effects, DNA Repair genetics, Epistasis, Genetic drug effects, Epistasis, Genetic genetics, Female, Humans, Oncogenes drug effects, Oncogenes genetics, Ovarian Neoplasms drug therapy, Ovarian Neoplasms genetics, Phenotype, Poly (ADP-Ribose) Polymerase-1, Poly(ADP-ribose) Polymerases genetics, Antineoplastic Agents pharmacology, Apoptosis genetics, Cell Division genetics, Neoplasms drug therapy, Neoplasms genetics, Signal Transduction genetics
Abstract

Following DNA damage, cells activate a complex DNA-damage-response (DDR) signaling network to arrest the cell cycle, repair DNA and, if the extend of damage is beyond repair capacity, induce apoptosis. DDR genes are among the most commonly mutated genes in human cancer and it is believed that these lesions promote a "MUTATOR-PHENOTYPE" that fuels the runaway proliferation of cancer cells. However, these genetic lesions can also be seen as the "Achilles heel" of cancer. These tumor cell-specific vulnerabilities are of extraordinary clinical interest, since they allow genetically-guided novel therapeutic regimens for the treatment of cancer. Here, we discuss such a novel therapeutic concept - synthetic lethality. We focus on the first successful clinical applications of synthetic lethality for the treatment of different cancer entities. In addition, we give a brief review of recently developed, synthetic lethality-based approaches that are close to clinical testing., (© Georg Thieme Verlag KG Stuttgart · New York.)

Published
2011
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