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Book ; Online ; E-Book: Tumor liquid biopsies

Schaffner, Florence / Merlin, Jean-Louis / Von Bubnoff, Nikolas

(Recent results in cancer research ; 215)

2020

Author's details	Florence Schaffner, Jean-Louis Merlin, Nikolas von Bubnoff editors
Series title	Recent results in cancer research ; 215
Collection
Keywords	Oncology ; Pathology ; Cancer research
Subject code	616.994
Language	English
Size	1 Online-Ressource (vi, 368 Seiten), Illustrationen
Publisher	Springer
Publishing place	Cham
Publishing country	Switzerland
Document type	Book ; Online ; E-Book
Remark	Zugriff für angemeldete ZB MED-Nutzerinnen und -Nutzer
HBZ-ID	HT020329211
ISBN	978-3-030-26439-0 ; 9783030264383 ; 3-030-26439-4 ; 3030264386
DOI	10.1007/978-3-030-26439-0
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Article: Real-World Electronic Medical Records Data Identify Risk Factors for Myelofibrosis and Can Be Used to Validate Established Prognostic Scores.

Kappenstein, Max / von Bubnoff, Nikolas

Cancers

2024 Volume 16, Issue 7

Abstract: Myelofibrosis (MF) is a myeloproliferative neoplasia arising de novo as primary myelofibrosis (PMF) or secondary to polycythemia vera or essential thrombocythemia. Patients experience a high symptom burden and a marked reduction in life expectancy. ... ...

Abstract	Myelofibrosis (MF) is a myeloproliferative neoplasia arising de novo as primary myelofibrosis (PMF) or secondary to polycythemia vera or essential thrombocythemia. Patients experience a high symptom burden and a marked reduction in life expectancy. Despite progress in molecular understanding and treatment, the clinical and prognostic heterogeneity of MF complicates treatment decisions. The International Prognostic Scoring System (IPSS) integrates clinical factors for risk stratification in MF. This study leverages the TriNetX database with more than 64,000 MF patients to assess the impact of accessible parameters on survival and complicating events, including AML transformation, cachexia, increased systemic inflammation, thrombosis and hemorrhage. Age over 65 years correlated with increased risks of death, AML transformation, thrombosis and hemorrhage. Anemia (Hb < 10 g/dL), leukocytosis (>25 × 10
Language	English
Publishing date	2024-04-05
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers16071416
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Article ; Online: Liquid Biopsy: Approaches to Dynamic Genotyping in Cancer.

von Bubnoff, Nikolas

Oncology research and treatment

2017 Volume 40, Issue 7-8, Page(s) 409–416

Abstract: Malignant tumors release tumor cells and fragments of nucleic acids into the bloodstream. Liquid biopsies are non-invasive blood tests that detect circulating tumor cells (CTC) and circulating nucleic acids such as mRNA, microRNA, and cell-free ... ...

Abstract	Malignant tumors release tumor cells and fragments of nucleic acids into the bloodstream. Liquid biopsies are non-invasive blood tests that detect circulating tumor cells (CTC) and circulating nucleic acids such as mRNA, microRNA, and cell-free circulating tumor DNA, also known as ctDNA. The presence of ctDNA or CTCs in the plasma has prognostic impact. Since ctDNA contains tumor-specific mutations, its detection in the blood or other body fluids can predict response to treatment and relapse. Moreover, repeated analysis and quantitation of ctDNA can inform about changes in clonal composition over time and thus allow dynamic treatment stratification. Today, the routine clinical use of liquid biopsy diagnostic tests is limited; however, in the near future, they might become commonly used sensitive and specific biomarkers to guide cancer treatment. This review will summarize recent findings on the use of ctDNA for monitoring response to therapy and dynamic genetic treatment stratification.
MeSH term(s)	Circulating Tumor DNA/blood ; Circulating Tumor DNA/genetics ; DNA Mutational Analysis ; Forecasting ; Genotyping Techniques/methods ; Genotyping Techniques/trends ; Humans ; Liquid Biopsy/methods ; Molecular Diagnostic Techniques/methods ; Neoplasms/genetics ; Neoplasms/pathology ; Neoplasms/therapy ; Neoplastic Cells, Circulating ; Prognosis ; Treatment Outcome
Chemical Substances	Circulating Tumor DNA
Language	English
Publishing date	2017-07-13
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2760274-6
ISSN	2296-5262 ; 2296-5270
ISSN (online)	2296-5262
ISSN	2296-5270
DOI	10.1159/000478864
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The Clinical Features of Hereditary Alpha-Tryptasemia—Implications for Interdisciplinary Practice.

von Bubnoff, Dagmar / Koch, Daniel / Stocker, Hannah / Ludwig, Ralf J / Wortmann, Friederike / von Bubnoff, Nikolas

Deutsches Arzteblatt international

2024 , Issue Forthcoming

Abstract: Background: Hereditary alpha-tryptasemia (HAT) is a genetic predisposition of autosomal dominant inheritance that leads to a high normal (≥ 8-11.4 μg/L) or pathologically elevated (>11.4 μg/L) basal serum tryptase (BST) concentration. Its prevalence in ... ...

Abstract	Background: Hereditary alpha-tryptasemia (HAT) is a genetic predisposition of autosomal dominant inheritance that leads to a high normal (≥ 8-11.4 μg/L) or pathologically elevated (>11.4 μg/L) basal serum tryptase (BST) concentration. Its prevalence in the United Kingdom and France is reportedly 5%-6%; its prevalence in Germany is unknown. Symptomatic persons with HAT suffer from a complex constellation of symptoms. As described in this review, HAT is an important differential diagnosis in interdisciplinary practice. Methods: This review is based on publications about HAT retrieved by a selective search in PubMed, on relevant presentations at scientific meetings, and on our clinical experience. We also collected our own data on the prevalence and clinical manifestations of HAT. Results: According to the literature, HAT is very common among patients in medical centers with BST values of 8 μg/L or above (64-74%). HAT is most commonly associated with neuropsychiatric symptoms such as exhaustion (85%), depressive episodes (59%), sleep disturbances (69%), and memory impairment (59%-68%), followed by gastrointestinal symptoms such as irritable bowel (30%-60%), nausea (51%), and reflux (49%-77%). Typical mast cell-mediated symptoms, such as flushing (47%), itch (69%), urticaria (37%), and anaphylaxis (14%-28%), are reported as well. Less commonly reported are cardiovascular manifestations, such as hypotonia, dizziness, and tachycardia (34%), and joint hypermobility (28%). HAT is more common among patients with sytemic mastocytosis (SM; 12%-21%). It is often associated with severe anaphylaxis induced by insect toxins or unknown triggers. The therapeutic options include treatment with antihistamines, mast-cell stabilizers, or IgE antibodies. Conclusion: A diagnosis of hereditary alpha-tryptasemia can be strongly suspected on the basis of thorough history-taking and BST measurement and then confirmed by molecular genetic testing.
Language	English
Publishing date	2024-03-22
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	2406159-1
ISSN	1866-0452 ; 1866-0452
ISSN (online)	1866-0452
ISSN	1866-0452
DOI	10.3238/arztebl.m2023.0287
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Article ; Online: Near complete remission of an inoperable pancreatic acinar cell carcinoma after BRAF-/MEK-inhibitor treatment-A case report and review of the literature.

von Fritsch, Lennart / von Bubnoff, Nikolas / Weber, Klaus / Kirfel, Jutta / Schreiber, Cleopatra / Keck, Tobias / Wellner, Ulrich

Genes, chromosomes & cancer

2024 Volume 63, Issue 2, Page(s) e23222

Abstract: Introduction: Pancreatic acinar cell carcinomas are rare malignant neoplasms. High-quality evidence about the best treatment strategy is lacking. We present the case of a 52-year-old male with a BRAF: Case: The patient presented with upper abdomen ... ...

Abstract	Introduction: Pancreatic acinar cell carcinomas are rare malignant neoplasms. High-quality evidence about the best treatment strategy is lacking. We present the case of a 52-year-old male with a BRAF Case: The patient presented with upper abdomen pain, night sweat, and weight loss. CT scan showed a pancreatic tumor extending from the pancreas head to body. Histological workup identified an acinar cell carcinoma. As the tumor was inoperable, chemotherapy with FOFIRNIOX was initiated and initially showed a slight regression of disease. The regimen had to be discontinued due to severe side effects. Molecular analysis identified a BRAF Discussion: Studies suggest that up to one-fourth of PACCs carry a BRAF mutation and might therefore be susceptible to a BRAF-/MEK-inhibitor therapy. This offers a new therapeutic pathway to treat this rare but malignant neoplasm.
MeSH term(s)	Humans ; Male ; Middle Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Carcinoma, Acinar Cell/drug therapy ; Carcinoma, Acinar Cell/genetics ; Carcinoma, Acinar Cell/chemically induced ; Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors ; Mutation ; Pancreatic Neoplasms/drug therapy ; Pancreatic Neoplasms/genetics ; Protein Kinase Inhibitors/therapeutic use ; Proto-Oncogene Proteins B-raf/antagonists & inhibitors ; Pyridones/pharmacology ; Pyrimidinones/pharmacology
Chemical Substances	BRAF protein, human (EC 2.7.11.1) ; Mitogen-Activated Protein Kinase Kinases (EC 2.7.12.2) ; Protein Kinase Inhibitors ; Proto-Oncogene Proteins B-raf (EC 2.7.11.1) ; Pyridones ; Pyrimidinones
Language	English
Publishing date	2024-02-05
Publishing country	United States
Document type	Review ; Case Reports ; Journal Article
ZDB-ID	1018988-9
ISSN	1098-2264 ; 1045-2257
ISSN (online)	1098-2264
ISSN	1045-2257
DOI	10.1002/gcc.23222
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Ponatinib: A Third-Generation Inhibitor for the Treatment of CML.

Wehrle, Julius / von Bubnoff, Nikolas

Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer

2018 Volume 212, Page(s) 109–118

Abstract: The establishment of imatinib as the standard therapy for CML marked the beginning of a new era of treatment. Due to occurring intolerance and resistance against the drug, the development of new inhibitors was promoted. This led to the second-generation ... ...

Abstract	The establishment of imatinib as the standard therapy for CML marked the beginning of a new era of treatment. Due to occurring intolerance and resistance against the drug, the development of new inhibitors was promoted. This led to the second-generation inhibitors dasatinib, nilotinib, and bosutinib. Despite all achieved improvements, first- and second-generation inhibitors are ineffective against the BCR-ABL T315I "gatekeeper" mutation. In order to overcome this issue and to further improve the inhibitory effect, the third-generation inhibitor ponatinib was developed. Various clinical trials have been launched to study the effect of ponatinib in the clinical setting. Based on positive phase 1 and phase 2 trials, ponatinib was approved for the second-line treatment of CML and Ph
MeSH term(s)	Antineoplastic Agents/pharmacology ; Clinical Trials, Phase I as Topic ; Clinical Trials, Phase II as Topic ; Drug Resistance, Neoplasm ; Humans ; Imidazoles/pharmacology ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy ; Protein Kinase Inhibitors/pharmacology ; Pyridazines/pharmacology
Chemical Substances	Antineoplastic Agents ; Imidazoles ; Protein Kinase Inhibitors ; Pyridazines ; ponatinib (4340891KFS)
Language	English
Publishing date	2018-08-02
Publishing country	Germany
Document type	Journal Article
ISSN	0080-0015
ISSN	0080-0015
DOI	10.1007/978-3-319-91439-8_5
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Article ; Online: Ruxolitinib for Acute Graft-versus-Host Disease. Reply.

Zeiser, Robert / von Bubnoff, Nikolas / Socié, Gérard

The New England journal of medicine

2020 Volume 383, Issue 5

MeSH term(s)	Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Pyrazoles
Chemical Substances	Pyrazoles ; ruxolitinib (82S8X8XX8H)
Language	English
Publishing date	2020-07-28
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJMc2020763
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Article ; Online: Tailored Systemic Therapy for Colorectal Cancer Liver Metastases.

Czauderna, Carolin / Luley, Kim / von Bubnoff, Nikolas / Marquardt, Jens U

International journal of molecular sciences

2021 Volume 22, Issue 21

Abstract: Liver metastases are the most common site of metastatic spread in colorectal cancer. Current treatment approaches involve effective systemic therapies in combination with surgical and/or interventional strategies. Multimodal strategies greatly improved ... ...

Abstract	Liver metastases are the most common site of metastatic spread in colorectal cancer. Current treatment approaches involve effective systemic therapies in combination with surgical and/or interventional strategies. Multimodal strategies greatly improved clinical outcomes of patients with metastatic colorectal cancer over the last decades. Identification of predictive and prognostic biomarkers helped to comprehensively refine individual targeted treatment approaches and resulted in median overall survival rates of 30 months or longer. Current guidelines, thus, recommend treatment selection according to patients' performance status, tumor localization and stage as well as the tumor's molecular and genetic status. Here, we outline the latest developments in molecular decision-making for patients with upfront resectable, potentially or initially unresectable and non/never-resectable colorectal cancer liver metastases.
MeSH term(s)	Animals ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Colorectal Neoplasms/diagnosis ; Colorectal Neoplasms/pathology ; Colorectal Neoplasms/therapy ; Disease Management ; Humans ; Immune Checkpoint Inhibitors/therapeutic use ; Liver/drug effects ; Liver/pathology ; Liver Neoplasms/diagnosis ; Liver Neoplasms/pathology ; Liver Neoplasms/secondary ; Liver Neoplasms/therapy ; Prognosis
Chemical Substances	Immune Checkpoint Inhibitors
Language	English
Publishing date	2021-10-29
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/ijms222111780
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Article ; Online: A newly identified 45-kDa JAK2 variant with an altered kinase domain structure represents a novel mode of JAK2 kinase inhibitor resistance.

Gorantla, Sivahari Prasad / Mueller, Tony Andreas / Albers-Leischner, Corinna / Rudelius, Martina / von Bubnoff, Nikolas / Duyster, Justus

Molecular oncology

2023 Volume 18, Issue 2, Page(s) 415–430

Abstract: Tyrosine-protein kinase (janus kinase; JAK)-signal transducer and activator of transcription (STAT) signaling plays a pivotal role in the development of myeloproliferative neoplasms (MPNs). Treatment with the potent JAK1/JAK2-specific inhibitor, ... ...

Abstract	Tyrosine-protein kinase (janus kinase; JAK)-signal transducer and activator of transcription (STAT) signaling plays a pivotal role in the development of myeloproliferative neoplasms (MPNs). Treatment with the potent JAK1/JAK2-specific inhibitor, ruxolitinib, significantly reduces tumor burden; however, ruxolitinib treatment does not fully eradicate the malignant clone. As the molecular basis for the disease persistence is not well understood, we set out to gain new insights by generating ruxolitinib-resistant cell lines. Surprisingly, these cells harbor a 45 kDa JAK2 variant (FERM-JAK2) consisting of the N-terminal FERM domain directly fused to the C-terminal kinase domain in 80% of sublines resistant to ruxolitinib. At the molecular level, FERM-JAK2 is able to directly bind and activate STAT5 in the absence of cytokine receptors. Furthermore, phosphorylation of activation-loop tyrosines is dispensable for FERM-JAK2-mediated STAT5 activation and cellular transformation, in contrast to JAK2-V617F. As a result, FERM-JAK2 is highly resistant to several ATP-competitive JAK2 inhibitors, whereas it is particularly sensitive to HSP90 inhibition. A murine model of FERM-JAK2 leukemogenesis showed an accelerated MPN phenotype with pronounced splenomegaly. Notably, most current protocols for the monitoring of emerging JAK variants are unable to detect FERM-JAK2, highlighting the urgent need for implementing next-generation sequencing approaches in MPN patients receiving ruxolitinib.
MeSH term(s)	Animals ; Humans ; Mice ; Antineoplastic Agents ; Janus Kinase 2/metabolism ; Janus Kinases/metabolism ; Nitriles/pharmacology ; Protein Kinase Inhibitors/pharmacology ; Pyrazoles/pharmacology ; Pyrimidines/pharmacology ; STAT5 Transcription Factor/genetics ; STAT5 Transcription Factor/metabolism
Chemical Substances	Antineoplastic Agents ; JAK2 protein, human (EC 2.7.10.2) ; Janus Kinase 2 (EC 2.7.10.2) ; Janus Kinases (EC 2.7.10.2) ; Nitriles ; Protein Kinase Inhibitors ; Pyrazoles ; Pyrimidines ; ruxolitinib (82S8X8XX8H) ; STAT5 Transcription Factor
Language	English
Publishing date	2023-12-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	2415106-3
ISSN	1878-0261 ; 1574-7891
ISSN (online)	1878-0261
ISSN	1574-7891
DOI	10.1002/1878-0261.13566
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Article: Liquid Biopsy: Approaches to Dynamic Genotyping in Cancer

von Bubnoff, Nikolas

Oncology Research and Treatment

2017 Volume 40, Issue 7-8, Page(s) 409–416

Institution	Department of Hematology, Oncology and Stem Cell Transplantation, Medical Center University of Freiburg, Freiburg i.Br., Germany German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany
Abstract	Malignant tumors release tumor cells and fragments of nucleic acids into the bloodstream. Liquid biopsies are non-invasive blood tests that detect circulating tumor cells (CTC) and circulating nucleic acids such as mRNA, microRNA, and cell-free circulating tumor DNA, also known as ctDNA. The presence of ctDNA or CTCs in the plasma has prognostic impact. Since ctDNA contains tumor-specific mutations, its detection in the blood or other body fluids can predict response to treatment and relapse. Moreover, repeated analysis and quantitation of ctDNA can inform about changes in clonal composition over time and thus allow dynamic treatment stratification. Today, the routine clinical use of liquid biopsy diagnostic tests is limited; however, in the near future, they might become commonly used sensitive and specific biomarkers to guide cancer treatment. This review will summarize recent findings on the use of ctDNA for monitoring response to therapy and dynamic genetic treatment stratification.
Keywords	Liquid biopsy ; Biomarker ; Molecular diagnosis
Language	English
Publishing date	2017-07-13
Publisher	S. Karger GmbH
Publishing place	Freiburg, Germany
Document type	Article
Note	Review Article
ZDB-ID	2760274-6
ISSN	2296-5262 ; 2296-5270
ISSN (online)	2296-5262
ISSN	2296-5270
DOI	10.1159/000478864
Database	Karger publisher's database

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