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  1. Article ; Online: Re-Sensitizing Tumor Cells to Cancer Drugs with Epigenetic Regulators.

    Rauscher, Stefanie / Greil, Richard / Geisberger, Roland

    Current cancer drug targets

    2021  Volume 21, Issue 4, Page(s) 353–359

    Abstract: Cancer drug resistance is a major problem for cancer therapy. While many drugs can be effective in first-line treatments, cancer cells can become resistant due to genetic (mutations and chromosomal aberrations) but also epigenetic changes. Hence, many ... ...

    Abstract Cancer drug resistance is a major problem for cancer therapy. While many drugs can be effective in first-line treatments, cancer cells can become resistant due to genetic (mutations and chromosomal aberrations) but also epigenetic changes. Hence, many research studies addressed epigenetic drugs in circumventing resistance to conventional therapeutics in different tumor entities and in increasing the efficiency of immune checkpoint therapies. Furthermore, repositioning of already approved drugs in combination with epigenetic modifiers could potentiate their efficacy and thus could be an attractive strategy for cancer treatment. Summarizing, we recapitulate current data on epigenetic drugs and their targets in modulating sensitivity towards conventional and immune therapies, providing evidence that altering expression profiles by epigenetic modifiers holds great potential to improve the clinical outcome of cancer patients.
    MeSH term(s) Antineoplastic Agents/classification ; Antineoplastic Agents/pharmacology ; Drug Discovery ; Drug Repositioning ; Drug Resistance, Neoplasm/genetics ; Drug Therapy, Combination/methods ; Drug Therapy, Combination/trends ; Epigenesis, Genetic/drug effects ; Gene Expression Regulation, Neoplastic ; Histone Code/drug effects ; Histone Code/physiology ; Humans ; Neoplasms/drug therapy ; Neoplasms/genetics ; Neoplasms/metabolism
    Chemical Substances Antineoplastic Agents
    Language English
    Publishing date 2021-01-12
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2064824-8
    ISSN 1873-5576 ; 1568-0096
    ISSN (online) 1873-5576
    ISSN 1568-0096
    DOI 10.2174/1568009620666210108102723
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5589: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (2.OG)
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  2. Article ; Online: CAR T-Cell Therapy in Hematological Malignancies.

    Haslauer, Theresa / Greil, Richard / Zaborsky, Nadja / Geisberger, Roland

    International journal of molecular sciences

    2021  Volume 22, Issue 16

    Abstract: Chimeric antigen receptor (CAR) T-cells (CAR T-cells) are a promising therapeutic approach in treating hematological malignancies. CAR T-cells represent engineered autologous T-cells, expressing a synthetic CAR, targeting tumor-associated antigens (TAAs) ...

    Abstract Chimeric antigen receptor (CAR) T-cells (CAR T-cells) are a promising therapeutic approach in treating hematological malignancies. CAR T-cells represent engineered autologous T-cells, expressing a synthetic CAR, targeting tumor-associated antigens (TAAs) independent of major histocompatibility complex (MHC) presentation. The most common target is CD19 on B-cells, predominantly used for the treatment of lymphoma and acute lymphocytic leukemia (ALL), leading to approval of five different CAR T-cell therapies for clinical application. Despite encouraging clinical results, treatment of other hematological malignancies such as acute myeloid leukemia (AML) remains difficult. In this review, we focus especially on CAR T-cell application in different hematological malignancies as well as strategies for overcoming CAR T-cell dysfunction and increasing their efficacy.
    MeSH term(s) Antigens, Neoplasm/immunology ; Hematologic Neoplasms/metabolism ; Hematologic Neoplasms/pathology ; Hematologic Neoplasms/therapy ; Humans ; Immunotherapy/methods ; Immunotherapy, Adoptive/methods ; Immunotherapy, Adoptive/trends ; Leukemia/immunology ; Leukemia/therapy ; Lymphoma/immunology ; Lymphoma/therapy ; Receptors, Antigen, T-Cell/immunology ; Receptors, Chimeric Antigen/immunology ; T-Lymphocytes/immunology
    Chemical Substances Antigens, Neoplasm ; Receptors, Antigen, T-Cell ; Receptors, Chimeric Antigen
    Language English
    Publishing date 2021-08-20
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms22168996
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: miRNA-Based Therapeutics in the Era of Immune-Checkpoint Inhibitors.

    Huemer, Florian / Leisch, Michael / Geisberger, Roland / Zaborsky, Nadja / Greil, Richard

    Pharmaceuticals (Basel, Switzerland)

    2021  Volume 14, Issue 2

    Abstract: MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by binding to complementary target regions on gene transcripts. Thus, miRNAs fine-tune gene expression profiles in a cell-type-specific manner and thereby regulate important ... ...

    Abstract MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by binding to complementary target regions on gene transcripts. Thus, miRNAs fine-tune gene expression profiles in a cell-type-specific manner and thereby regulate important cellular functions, such as cell growth, proliferation and cell death. MiRNAs are frequently dysregulated in cancer cells by several mechanisms, which significantly affect the course of the disease. In this review, we summarize the current knowledge on how dysregulated miRNAs contribute to cancer and how miRNAs can be exploited as predictive factors and therapeutic targets, particularly in regard to immune-checkpoint inhibitor therapies.
    Language English
    Publishing date 2021-01-26
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2193542-7
    ISSN 1424-8247
    ISSN 1424-8247
    DOI 10.3390/ph14020089
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: CAR T-Cell Therapy in Hematological Malignancies

    Theresa Haslauer / Richard Greil / Nadja Zaborsky / Roland Geisberger

    International Journal of Molecular Sciences, Vol 22, Iss 8996, p

    2021  Volume 8996

    Abstract: Chimeric antigen receptor (CAR) T-cells (CAR T-cells) are a promising therapeutic approach in treating hematological malignancies. CAR T-cells represent engineered autologous T-cells, expressing a synthetic CAR, targeting tumor-associated antigens (TAAs) ...

    Abstract Chimeric antigen receptor (CAR) T-cells (CAR T-cells) are a promising therapeutic approach in treating hematological malignancies. CAR T-cells represent engineered autologous T-cells, expressing a synthetic CAR, targeting tumor-associated antigens (TAAs) independent of major histocompatibility complex (MHC) presentation. The most common target is CD19 on B-cells, predominantly used for the treatment of lymphoma and acute lymphocytic leukemia (ALL), leading to approval of five different CAR T-cell therapies for clinical application. Despite encouraging clinical results, treatment of other hematological malignancies such as acute myeloid leukemia (AML) remains difficult. In this review, we focus especially on CAR T-cell application in different hematological malignancies as well as strategies for overcoming CAR T-cell dysfunction and increasing their efficacy.
    Keywords CAR T-cells ; hematological malignancies ; leukemia ; lymphoma ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Language English
    Publishing date 2021-08-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Validation of genetic variants from NGS data using deep convolutional neural networks.

    Vaisband, Marc / Schubert, Maria / Gassner, Franz Josef / Geisberger, Roland / Greil, Richard / Zaborsky, Nadja / Hasenauer, Jan

    BMC bioinformatics

    2023  Volume 24, Issue 1, Page(s) 158

    Abstract: Accurate somatic variant calling from next-generation sequencing data is one most important tasks in personalised cancer therapy. The sophistication of the available technologies is ever-increasing, yet, manual candidate refinement is still a necessary ... ...

    Abstract Accurate somatic variant calling from next-generation sequencing data is one most important tasks in personalised cancer therapy. The sophistication of the available technologies is ever-increasing, yet, manual candidate refinement is still a necessary step in state-of-the-art processing pipelines. This limits reproducibility and introduces a bottleneck with respect to scalability. We demonstrate that the validation of genetic variants can be improved using a machine learning approach resting on a Convolutional Neural Network, trained using existing human annotation. In contrast to existing approaches, we introduce a way in which contextual data from sequencing tracks can be included into the automated assessment. A rigorous evaluation shows that the resulting model is robust and performs on par with trained researchers following published standard operating procedure.
    MeSH term(s) Humans ; Reproducibility of Results ; Neural Networks, Computer ; Machine Learning ; High-Throughput Nucleotide Sequencing/methods
    Language English
    Publishing date 2023-04-20
    Publishing country England
    Document type Journal Article
    ZDB-ID 2041484-5
    ISSN 1471-2105 ; 1471-2105
    ISSN (online) 1471-2105
    ISSN 1471-2105
    DOI 10.1186/s12859-023-05255-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Detecting Bacterial-Human Lateral Gene Transfer in Chronic Lymphocytic Leukemia.

    Akimova, Ekaterina / Gassner, Franz Josef / Greil, Richard / Zaborsky, Nadja / Geisberger, Roland

    International journal of molecular sciences

    2022  Volume 23, Issue 3

    Abstract: Chronic lymphocytic leukemia (CLL) is a very common and mostly incurable B-cell malignancy. Recent studies revealed high interpatient mutational heterogeneity and worsened therapy response and survival of patients with complex genomic aberrations. In ... ...

    Abstract Chronic lymphocytic leukemia (CLL) is a very common and mostly incurable B-cell malignancy. Recent studies revealed high interpatient mutational heterogeneity and worsened therapy response and survival of patients with complex genomic aberrations. In line with this, a better understanding of the underlying mechanisms of specific genetic aberrations would reveal new prognostic factors and possible therapeutic targets. It is known that chromosomal rearrangements including DNA insertions often play a role during carcinogenesis. Recently it was reported that bacteria (microbiome)-human lateral gene transfer occurs in somatic cells and is enriched in cancer samples. To further investigate this mechanism in CLL, we analyzed paired-end RNA sequencing data of 45 CLL patients and 9 healthy donors, in which we particularly searched for bacterial DNA integrations into the human somatic genome. Applying the Burrows-Wheeler aligner (BWA) first on a human genome and then on bacterial genome references, we differentiated between sequencing reads mapping to the human genome, to the microbiome or to bacterial integrations into the human genome. Our results indicate that CLL samples featured bacterial DNA integrations more frequently (approx. two-fold) compared to normal samples, which corroborates the latest findings in other cancer entities. Moreover, we determined common integration sites and recurrent integrated bacterial transcripts. Finally, we investigated the contribution of bacterial integrations to oncogenesis and disease progression.
    MeSH term(s) Bacteria/genetics ; Bacteria/growth & development ; Case-Control Studies ; Chromosome Aberrations ; Gene Transfer, Horizontal ; Genome, Bacterial ; Genome, Human ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/genetics ; Leukemia, Lymphocytic, Chronic, B-Cell/microbiology ; Leukemia, Lymphocytic, Chronic, B-Cell/pathology ; Microbiota
    Language English
    Publishing date 2022-01-20
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms23031094
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Risks and chances of aberrant DNA repair in cancer.

    Schubert, Maria / Greil, Richard / Geisberger, Roland

    Oncoscience

    2018  Volume 5, Issue 9-10, Page(s) 256–257

    Language English
    Publishing date 2018-08-22
    Publishing country United States
    Document type Journal Article
    ISSN 2331-4737
    ISSN 2331-4737
    DOI 10.18632/oncoscience.459
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: miRNA-Based Therapeutics in the Era of Immune-Checkpoint Inhibitors

    Florian Huemer / Michael Leisch / Roland Geisberger / Nadja Zaborsky / Richard Greil

    Pharmaceuticals, Vol 14, Iss 2, p

    2021  Volume 89

    Abstract: MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by binding to complementary target regions on gene transcripts. Thus, miRNAs fine-tune gene expression profiles in a cell-type-specific manner and thereby regulate important ... ...

    Abstract MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by binding to complementary target regions on gene transcripts. Thus, miRNAs fine-tune gene expression profiles in a cell-type-specific manner and thereby regulate important cellular functions, such as cell growth, proliferation and cell death. MiRNAs are frequently dysregulated in cancer cells by several mechanisms, which significantly affect the course of the disease. In this review, we summarize the current knowledge on how dysregulated miRNAs contribute to cancer and how miRNAs can be exploited as predictive factors and therapeutic targets, particularly in regard to immune-checkpoint inhibitor therapies.
    Keywords miRNA ; microRNA ; immune-checkpoint inhibitor ; immune-checkpoint blockade ; predictive ; ipilimumab ; Medicine ; R ; Pharmacy and materia medica ; RS1-441
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Detecting Bacterial–Human Lateral Gene Transfer in Chronic Lymphocytic Leukemia

    Ekaterina Akimova / Franz Josef Gassner / Richard Greil / Nadja Zaborsky / Roland Geisberger

    International Journal of Molecular Sciences, Vol 23, Iss 1094, p

    2022  Volume 1094

    Abstract: Chronic lymphocytic leukemia (CLL) is a very common and mostly incurable B-cell malignancy. Recent studies revealed high interpatient mutational heterogeneity and worsened therapy response and survival of patients with complex genomic aberrations. In ... ...

    Abstract Chronic lymphocytic leukemia (CLL) is a very common and mostly incurable B-cell malignancy. Recent studies revealed high interpatient mutational heterogeneity and worsened therapy response and survival of patients with complex genomic aberrations. In line with this, a better understanding of the underlying mechanisms of specific genetic aberrations would reveal new prognostic factors and possible therapeutic targets. It is known that chromosomal rearrangements including DNA insertions often play a role during carcinogenesis. Recently it was reported that bacteria (microbiome)–human lateral gene transfer occurs in somatic cells and is enriched in cancer samples. To further investigate this mechanism in CLL, we analyzed paired-end RNA sequencing data of 45 CLL patients and 9 healthy donors, in which we particularly searched for bacterial DNA integrations into the human somatic genome. Applying the Burrows–Wheeler aligner (BWA) first on a human genome and then on bacterial genome references, we differentiated between sequencing reads mapping to the human genome, to the microbiome or to bacterial integrations into the human genome. Our results indicate that CLL samples featured bacterial DNA integrations more frequently (approx. two-fold) compared to normal samples, which corroborates the latest findings in other cancer entities. Moreover, we determined common integration sites and recurrent integrated bacterial transcripts. Finally, we investigated the contribution of bacterial integrations to oncogenesis and disease progression.
    Keywords CLL ; lateral gene transfer (LGT) ; bacterial integrations ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 572
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Oncogenic MTOR signaling axis compensates BTK inhibition in a Chronic Lymphocytic Leukemia patient with Richter Transformation: A Case Report and Review of the Literature.

    Parigger, Thomas / Drothler, Stephan / Scherhäufl, Christian / Gassner, Franz Josef / Schubert, Maria / Steiner, Markus / Höpner, Jan Philip / Hödlmoser, Alexandra / Schultheis, Lena / Abu Bakar, Aryunni / Neureiter, Daniel / Pleyer, Lisa / Egle, Alexander / Greil, Richard / Geisberger, Roland / Zaborsky, Nadja

    Acta haematologica

    2024  

    Abstract: Introduction: Targeting the B cell receptor (BCR) pathway via ibrutinib, a specific inhibitor of Bruton's tyrosine kinase, has shown marked clinical efficacy in treatment of patients with chronic lymphocytic leukemia (CLL), thus becoming a preferred ... ...

    Abstract Introduction: Targeting the B cell receptor (BCR) pathway via ibrutinib, a specific inhibitor of Bruton's tyrosine kinase, has shown marked clinical efficacy in treatment of patients with chronic lymphocytic leukemia (CLL), thus becoming a preferred first line option independent of risk factors. However, acquired resistance to ibrutinib poses a major clinical problem and requires the development of novel treatment combinations to increase efficacy and counteract resistance development and clinical relapse rates.
    Case presentation: In this study, we performed exome and transcriptome analyses of an ibrutinib resistant CLL patient in order to investigate genes and expression patterns associated with ibrutinib resistance. Here we provide evidence that ibrutinib resistance can be attributed to aberrant mammalian target of rapamycin (MTOR) signaling.
    Conclusion: Thus, our study proposes that combined use of MTOR inhibitors with ibrutinib could be a possible option to overcome therapy resistance in ibrutinib treated patients.
    Language English
    Publishing date 2024-02-24
    Publishing country Switzerland
    Document type Case Reports
    ZDB-ID 80008-9
    ISSN 1421-9662 ; 0001-5792
    ISSN (online) 1421-9662
    ISSN 0001-5792
    DOI 10.1159/000537791
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Ud II Zs.145: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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