Simvastatin enhances the efficacy of nilotinib in chronic myeloid leukaemia by post-translational modification and drug transporter modulation
The resistance of chronic myeloid leukaemia (CML) to tyrosine kinase inhibitors (TKIs) remains a significant clinical problem. Targeting alternative pathways, such as protein prenylation, is known to be effective in overcoming resistance. Simvastatin inhibits 3-hydroxy-3-methylglutaryl-CoA reductase (a key enzyme in isoprenoid-regulation), thereby inhibiting prenylation. We demonstrate that simvastatin alone effectively inhibits proliferation in a panel of TKI-resistant CML cell lines, regardless of mechanism of resistance. We further show that the combination of nilotinib and simvastatin synergistically kills CML cells vi...
Source: Anti-Cancer Drugs - April 16, 2021 Category: Cancer & Oncology Tags: Preclinical Reports Source Type: research

The Potential Safe Antifibrotic Effect of Stem Cell Conditioned Medium and Nilotinib Combined Therapy by Selective Elimination of Rat Activated HSCs
Biomed Res Int. 2021 Mar 28;2021:6678913. doi: 10.1155/2021/6678913. eCollection 2021.ABSTRACTHepatic fibrosis is a progressive disease with serious clinical complications that arise from abnormal propagation and activation of multiple inflammatory pathways. Nilotinib is an oral tyrosine kinase inhibitor with antifibrotic activity. Mesenchymal stem cells (MSCs) are blank cells and can differentiate into specific cell types. They have the potential to repair and regenerate cells. MSCs have a special paracrine fashion where they produce special exosomes, microvesicles, and cytokines like IL-6, transforming growth factor-beta...
Source: Biomed Res - April 15, 2021 Category: Research Authors: Ahmed Nabil Koichiro Uto Faten Zahran Reham Soliman Ayman A Hassan Mohamed M Elshemy Islam S Ali Mitsuhiro Ebara Gamal Shiha Source Type: research

Direct interaction of the ATP-sensitive K < sup > + < /sup > channel by the tyrosine kinase inhibitors imatinib, sunitinib and nilotinib
Biochem Biophys Res Commun. 2021 Apr 12;557:14-19. doi: 10.1016/j.bbrc.2021.03.166. Online ahead of print.ABSTRACTThe ATP-regulated K+ channel (KATP) plays an essential role in the control of many physiological processes, and contains a ATP-binding site. Tyrosine kinase inhibitors (TKI) are commonly used drugs, that primarily target ATP-binding sites in tyrosine kinases. Herein, we used the patch-clamp technique to examine the effects of three clinically established TKIs on KATP channel activity in isolated membrane patches, using a pancreatic β-cell line as a KATP channel source. In excised inside-out patches, the ac...
Source: Biochemical and Biophysical Research communications - April 15, 2021 Category: Biochemistry Authors: Robin Fr öbom Erik Berglund Craig A Aspinwall Weng-Onn Lui Inga-Lena Nilsson Catharina Larsson Robert Br änström Source Type: research

Fertility considerations in targeted biologic therapy with tyrosine kinase inhibitors: a review
ConclusionWomen should be advised to avoid conception while taking a TKI. Women on TKIs who are considering pregnancy should be encouraged to plan the pregnancy to minimize inadvertent first trimester exposure. In women who conceive while taking TKIs, the serious risk of relapse due to discontinuation of TKI should be balanced against the potential risks to the fetus. The risk of teratogenicity to a fathered pregnancy with TKI use is considerably lower. Fertility preservation for a woman taking a TKI can be considered to plan a pregnancy with a minimal TKI-free period. With careful monitoring, providers may consider a TKI ...
Source: Journal of Assisted Reproduction and Genetics - April 7, 2021 Category: Reproduction Medicine Source Type: research

Cancers, Vol. 13, Pages 1643: Meta-Analysis of Gastrointestinal Adverse Events from Tyrosine Kinase Inhibitors for Chronic Myeloid Leukemia
ta Cassie S. Mitchell Tyrosine kinase inhibitors (TKIs) are the frontline therapy for BCR-ABL (Ph+) chronic myeloid leukemia (CML). A systematic meta-analysis of 43 peer-reviewed studies with 10,769 CML patients compared the incidence of gastrointestinal adverse events (GI AEs) in a large heterogeneous CML population as a function of TKI type. Incidence and severity of nausea, vomiting, and diarrhea were assessed for imatinib, dasatinib, bosutinib, and nilotinib. Examination of combined TKI average GI AE incidence found diarrhea most prevalent (22.5%), followed by nausea (20.6%), and vomiting (12.9%). Other TKI GI AE...
Source: Cancers - April 1, 2021 Category: Cancer & Oncology Authors: Prahathishree Mohanavelu Mira Mutnick Nidhi Mehra Brandon White Sparsh Kudrimoti Kaci Hernandez Kluesner Xinyu Chen Tim Nguyen Elaina Horlander Helena Thenot Vamsi Kota Cassie S. Mitchell Tags: Article Source Type: research

Current status and novel strategy of CML
Int J Hematol. 2021 Mar 29. doi: 10.1007/s12185-021-03127-5. Online ahead of print.ABSTRACTThe advent of tyrosine kinase inhibitors (TKIs) has dramatically improved the outcome of patients with chronic myeloid leukemia (CML). Currently, four TKIs are available for the frontline treatment, including the first-generation TKI (imatinib) and the second-generation TKIs (dasatinib, nilotinib, and bosutinib). The second-generation TKIs lead to a faster and deeper molecular response without a survival benefit compared with imatinib. However, the opportunity for the treatment discontinuation and functional cure requires the achieve...
Source: International Journal of Hematology - March 30, 2021 Category: Hematology Authors: Kiyomi Morita Koji Sasaki Source Type: research

Current status and novel strategy of CML
Int J Hematol. 2021 Mar 29. doi: 10.1007/s12185-021-03127-5. Online ahead of print.ABSTRACTThe advent of tyrosine kinase inhibitors (TKIs) has dramatically improved the outcome of patients with chronic myeloid leukemia (CML). Currently, four TKIs are available for the frontline treatment, including the first-generation TKI (imatinib) and the second-generation TKIs (dasatinib, nilotinib, and bosutinib). The second-generation TKIs lead to a faster and deeper molecular response without a survival benefit compared with imatinib. However, the opportunity for the treatment discontinuation and functional cure requires the achieve...
Source: International Journal of Hematology - March 30, 2021 Category: Hematology Authors: Kiyomi Morita Koji Sasaki Source Type: research

Current status and novel strategy of CML
Int J Hematol. 2021 Mar 29. doi: 10.1007/s12185-021-03127-5. Online ahead of print.ABSTRACTThe advent of tyrosine kinase inhibitors (TKIs) has dramatically improved the outcome of patients with chronic myeloid leukemia (CML). Currently, four TKIs are available for the frontline treatment, including the first-generation TKI (imatinib) and the second-generation TKIs (dasatinib, nilotinib, and bosutinib). The second-generation TKIs lead to a faster and deeper molecular response without a survival benefit compared with imatinib. However, the opportunity for the treatment discontinuation and functional cure requires the achieve...
Source: International Journal of Hematology - March 30, 2021 Category: Hematology Authors: Kiyomi Morita Koji Sasaki Source Type: research

Current status and novel strategy of CML
Int J Hematol. 2021 Mar 29. doi: 10.1007/s12185-021-03127-5. Online ahead of print.ABSTRACTThe advent of tyrosine kinase inhibitors (TKIs) has dramatically improved the outcome of patients with chronic myeloid leukemia (CML). Currently, four TKIs are available for the frontline treatment, including the first-generation TKI (imatinib) and the second-generation TKIs (dasatinib, nilotinib, and bosutinib). The second-generation TKIs lead to a faster and deeper molecular response without a survival benefit compared with imatinib. However, the opportunity for the treatment discontinuation and functional cure requires the achieve...
Source: International Journal of Hematology - March 30, 2021 Category: Hematology Authors: Kiyomi Morita Koji Sasaki Source Type: research

Current status and novel strategy of CML
Int J Hematol. 2021 Mar 29. doi: 10.1007/s12185-021-03127-5. Online ahead of print.ABSTRACTThe advent of tyrosine kinase inhibitors (TKIs) has dramatically improved the outcome of patients with chronic myeloid leukemia (CML). Currently, four TKIs are available for the frontline treatment, including the first-generation TKI (imatinib) and the second-generation TKIs (dasatinib, nilotinib, and bosutinib). The second-generation TKIs lead to a faster and deeper molecular response without a survival benefit compared with imatinib. However, the opportunity for the treatment discontinuation and functional cure requires the achieve...
Source: International Journal of Hematology - March 30, 2021 Category: Hematology Authors: Kiyomi Morita Koji Sasaki Source Type: research

Current status and novel strategy of CML
Int J Hematol. 2021 Mar 29. doi: 10.1007/s12185-021-03127-5. Online ahead of print.ABSTRACTThe advent of tyrosine kinase inhibitors (TKIs) has dramatically improved the outcome of patients with chronic myeloid leukemia (CML). Currently, four TKIs are available for the frontline treatment, including the first-generation TKI (imatinib) and the second-generation TKIs (dasatinib, nilotinib, and bosutinib). The second-generation TKIs lead to a faster and deeper molecular response without a survival benefit compared with imatinib. However, the opportunity for the treatment discontinuation and functional cure requires the achieve...
Source: International Journal of Hematology - March 30, 2021 Category: Hematology Authors: Kiyomi Morita Koji Sasaki Source Type: research

Current status and novel strategy of CML
Int J Hematol. 2021 Mar 29. doi: 10.1007/s12185-021-03127-5. Online ahead of print.ABSTRACTThe advent of tyrosine kinase inhibitors (TKIs) has dramatically improved the outcome of patients with chronic myeloid leukemia (CML). Currently, four TKIs are available for the frontline treatment, including the first-generation TKI (imatinib) and the second-generation TKIs (dasatinib, nilotinib, and bosutinib). The second-generation TKIs lead to a faster and deeper molecular response without a survival benefit compared with imatinib. However, the opportunity for the treatment discontinuation and functional cure requires the achieve...
Source: International Journal of Hematology - March 30, 2021 Category: Hematology Authors: Kiyomi Morita Koji Sasaki Source Type: research

Current status and novel strategy of CML
Int J Hematol. 2021 Mar 29. doi: 10.1007/s12185-021-03127-5. Online ahead of print.ABSTRACTThe advent of tyrosine kinase inhibitors (TKIs) has dramatically improved the outcome of patients with chronic myeloid leukemia (CML). Currently, four TKIs are available for the frontline treatment, including the first-generation TKI (imatinib) and the second-generation TKIs (dasatinib, nilotinib, and bosutinib). The second-generation TKIs lead to a faster and deeper molecular response without a survival benefit compared with imatinib. However, the opportunity for the treatment discontinuation and functional cure requires the achieve...
Source: International Journal of Hematology - March 30, 2021 Category: Hematology Authors: Kiyomi Morita Koji Sasaki Source Type: research

Current status and novel strategy of CML
Int J Hematol. 2021 Mar 29. doi: 10.1007/s12185-021-03127-5. Online ahead of print.ABSTRACTThe advent of tyrosine kinase inhibitors (TKIs) has dramatically improved the outcome of patients with chronic myeloid leukemia (CML). Currently, four TKIs are available for the frontline treatment, including the first-generation TKI (imatinib) and the second-generation TKIs (dasatinib, nilotinib, and bosutinib). The second-generation TKIs lead to a faster and deeper molecular response without a survival benefit compared with imatinib. However, the opportunity for the treatment discontinuation and functional cure requires the achieve...
Source: International Journal of Hematology - March 30, 2021 Category: Hematology Authors: Kiyomi Morita Koji Sasaki Source Type: research

Current status and novel strategy of CML
Int J Hematol. 2021 Mar 29. doi: 10.1007/s12185-021-03127-5. Online ahead of print.ABSTRACTThe advent of tyrosine kinase inhibitors (TKIs) has dramatically improved the outcome of patients with chronic myeloid leukemia (CML). Currently, four TKIs are available for the frontline treatment, including the first-generation TKI (imatinib) and the second-generation TKIs (dasatinib, nilotinib, and bosutinib). The second-generation TKIs lead to a faster and deeper molecular response without a survival benefit compared with imatinib. However, the opportunity for the treatment discontinuation and functional cure requires the achieve...
Source: International Journal of Hematology - March 30, 2021 Category: Hematology Authors: Kiyomi Morita Koji Sasaki Source Type: research

Current status and novel strategy of CML
Int J Hematol. 2021 Mar 29. doi: 10.1007/s12185-021-03127-5. Online ahead of print.ABSTRACTThe advent of tyrosine kinase inhibitors (TKIs) has dramatically improved the outcome of patients with chronic myeloid leukemia (CML). Currently, four TKIs are available for the frontline treatment, including the first-generation TKI (imatinib) and the second-generation TKIs (dasatinib, nilotinib, and bosutinib). The second-generation TKIs lead to a faster and deeper molecular response without a survival benefit compared with imatinib. However, the opportunity for the treatment discontinuation and functional cure requires the achieve...
Source: International Journal of Hematology - March 30, 2021 Category: Hematology Authors: Kiyomi Morita Koji Sasaki Source Type: research

Targeting autophagy as a therapeutic strategy to prevent dopamine neuron loss in early stages of Alzheimer disease
Autophagy. 2021 Mar 28. doi: 10.1080/15548627.2021.1909409. Online ahead of print.ABSTRACTAlzheimer disease (AD) is a neurodegenerative disorder for which no approved medication exists. AD is characterized by worsening cognitive and non-cognitive symptoms, and research in the AD field strives to identify very precocious brain alterations leading to an irreversible condition. Recently it has been demonstrated that several early AD symptoms are paralleled with degeneration of neurons producing dopamine (DA), a neurotransmitter involved in the regulation of cognitive and non-cognitive functions. Actually, we found that ventra...
Source: Autophagy - March 29, 2021 Category: Cytology Authors: Annalisa Nobili Livia La Barbera Marcello D'Amelio Source Type: research

Cancers, Vol. 13, Pages 1566: UGT1A1 Guided Cancer Therapy: Review of the Evidence and Considerations for Clinical Implementation
lman J. Kevin Hicks Multi-gene assays often include UGT1A1 and, in certain instances, may report associated toxicity risks for irinotecan, belinostat, pazopanib, and nilotinib. However, guidance for incorporating UGT1A1 results into therapeutic decision-making is mostly lacking for these anticancer drugs. We summarized meta-analyses, genome-wide association studies, clinical trials, drug labels, and guidelines relating to the impact of UGT1A1 polymorphisms on irinotecan, belinostat, pazopanib, or nilotinib toxicities. For irinotecan, UGT1A1*28 was significantly associated with neutropenia and diarrhea, particularly w...
Source: Cancers - March 29, 2021 Category: Cancer & Oncology Authors: Ryan S. Nelson Nathan D. Seligson Sal Bottiglieri Estrella Carballido Alex Del Cueto Iman Imanirad Richard Levine Alexander S. Parker Sandra M. Swain Emma M. Tillman J. Kevin Hicks Tags: Review Source Type: research

High-throughput liquid chromatography/electrospray ionization tandem mass spectrometry method using in-source collision-induced dissociation for simultaneous quantification of imatinib, dasatinib, bosutinib, nilotinib, and ibrutinib in human plasma
In this study, we applied the in-source collision-induced dissociation technique to control the ion amounts in mass spectrometry. This new method allowed rapid determination within 5 min with simple pretreatment. The method was validated according to the US Food and Drug Administration guidelines. Moreover, all chronic leukemia patient samples were successfully measured and their values were within the linear range of measurement. Therefore, our high-throughput analytical system is useful to measure the plasma concentrations of imatinib, dasatinib, bosutinib, nilotinib, and ibrutinib in clinical practice.PMID:33772839 | DO...
Source: Biomedical Chromatography : BMC - March 27, 2021 Category: Biomedical Science Authors: Tensei Hirasawa Masafumi Kikuchi Kensuke Shigeta Shinya Takasaki Yu Sato Toshihiro Sato Jiro Ogura Koichi Onodera Noriko Fukuhara Yasushi Onishi Masamitsu Maekawa Nariyasu Mano Source Type: research

High-throughput liquid chromatography/electrospray ionization tandem mass spectrometry method using in-source collision-induced dissociation for simultaneous quantification of imatinib, dasatinib, bosutinib, nilotinib, and ibrutinib in human plasma
In this study, we applied the in-source collision-induced dissociation technique to control the ion amounts in mass spectrometry. This new method allowed rapid determination within 5 min with simple pretreatment. The method was validated according to the US Food and Drug Administration guidelines. Moreover, all chronic leukemia patient samples were successfully measured and their values were within the linear range of measurement. Therefore, our high-throughput analytical system is useful to measure the plasma concentrations of imatinib, dasatinib, bosutinib, nilotinib, and ibrutinib in clinical practice.PMID:33772839 | DO...
Source: Biomedical Chromatography : BMC - March 27, 2021 Category: Biomedical Science Authors: Tensei Hirasawa Masafumi Kikuchi Kensuke Shigeta Shinya Takasaki Yu Sato Toshihiro Sato Jiro Ogura Koichi Onodera Noriko Fukuhara Yasushi Onishi Masamitsu Maekawa Nariyasu Mano Source Type: research

High-throughput liquid chromatography/electrospray ionization tandem mass spectrometry method using in-source collision-induced dissociation for simultaneous quantification of imatinib, dasatinib, bosutinib, nilotinib, and ibrutinib in human plasma
In this study, we applied the in-source collision-induced dissociation technique to control the ion amounts in mass spectrometry. This new method allowed rapid determination within 5 min with simple pretreatment. The method was validated according to the US Food and Drug Administration guidelines. Moreover, all chronic leukemia patient samples were successfully measured and their values were within the linear range of measurement. Therefore, our high-throughput analytical system is useful to measure the plasma concentrations of imatinib, dasatinib, bosutinib, nilotinib, and ibrutinib in clinical practice.PMID:33772839 | DO...
Source: Biomedical Chromatography : BMC - March 27, 2021 Category: Biomedical Science Authors: Tensei Hirasawa Masafumi Kikuchi Kensuke Shigeta Shinya Takasaki Yu Sato Toshihiro Sato Jiro Ogura Koichi Onodera Noriko Fukuhara Yasushi Onishi Masamitsu Maekawa Nariyasu Mano Source Type: research

Dasatinib in the Management of Pediatric Patients With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia
Acute leukemia is the most common cancer in childhood; in particular, acute lymphoblastic leukemia (ALL) represents roughly up to 80% of all cases of acute leukemias in children. Survival of children with ALL has dramatically improved over the last few decades, and is now over 90% (versus 40% of adult patients) in developed countries, except for in infants (i.e., children
Source: Frontiers in Oncology - March 25, 2021 Category: Cancer & Oncology Source Type: research

Intracranial Hemorrhage in a Pediatric Patient with Chronic Myeloid Leukemia in Chronic Phase: A Case Report
We report the case of a 14-year-old female patient with CML-CP who developed ICH 8 days after admission. A 14-year-old girl developed symptoms of fatigue and slight fever and was diagnosed with CML-CP. She was treated with imatinib and received low-molecular-weight heparin owing to coagulation abnormalities. However, 6 days later, she developed sensorineural hearing loss, which is a symptom of leukostasis. She received hydroxyurea to reduce her white blood cell (WBC) count, and her treatment was changed from imatinib to nilotinib. The WBC and platelet counts remained unchanged, blast counts did not increase, and mild coagu...
Source: Case Reports in Oncology - March 22, 2021 Category: Cancer & Oncology Source Type: research

High ‐grade B‐cell lymphoma developed during the treatment of chronic myeloid leukemia with bosutinib
There remains no consensus on the management of secondary lymphoma during TKI therapies. The only alternative is to observe patients receiving TKI treatment cautiously and to treat secondary lymphoma in the same manner as de novo lymphoma. AbstractTyrosine kinase inhibitor (TKI) can help to increase the survival time in chronic myeloid leukemia (CML) patients; however, the risk of secondary malignancies due to TKIs is a growing concern. Only few reports showed clinical course of patients who developed lymphoma during TKI therapies. Herein, we report a case of high ‐grade B‐cell lymphoma diagnosed in the course of CML t...
Source: Clinical Case Reports - March 21, 2021 Category: General Medicine Authors: Teruhito Takakuwa, Ryota Sakai, Shiro Koh, Hiroshi Okamura, Satoru Nanno, Yasuhiro Nakashima, Takahiko Nakane, Hideo Koh, Masayuki Hino, Hirohisa Nakamae Tags: CASE REPORT Source Type: research

An indirect comparison between bosutinib, nilotinib and dasatinib in first-line chronic phase chronic myeloid leukemia
CONCLUSIONS: Overall, in these analyses bosutinib demonstrates equivalent efficacy to nilotinib and dasatinib in the treatment of patients with newly diagnosed CP-CML.PMID:33733983 | DOI:10.1080/03007995.2021.1896489 (Source: Current Medical Research and Opinion)
Source: Current Medical Research and Opinion - March 18, 2021 Category: Research Authors: Bogdan Muresan Carla Mamolo Joseph C Cappelleri Eric Leip Andrea Viqueira Bart Heeg Source Type: research

Chronic Myelogenous Leukemia in Childhood
AbstractPurpose of ReviewChronic myelogenous leukemia (CML) is rare in children, requiring extrapolation from treatment of adults. In this review, we explore similarities and differences between adult and pediatric CML with a focus on therapeutic advances and emerging clinical questions.Recent FindingsPediatric CML is effectively treated with long-term targeted therapy using tyrosine kinase inhibitors (TKIs). Newly diagnosed pediatric patients in chronic phase can now be treated with imatinib, dasatinib, or nilotinib without allogeneic hematopoietic stem cell transplantation. While treatment-free remission is possible in a...
Source: Current Oncology Reports - March 14, 2021 Category: Cancer & Oncology Source Type: research

Treatment-free remission following frontline nilotinib in patients with chronic phase chronic myeloid leukemia: 5-year update of the ENESTfreedom trial
Leukemia, Published online: 11 March 2021; doi:10.1038/s41375-021-01205-5Treatment-free remission following frontline nilotinib in patients with chronic phase chronic myeloid leukemia: 5-year update of the ENESTfreedom trial (Source: Leukemia)
Source: Leukemia - March 11, 2021 Category: Hematology Authors: Jerald P. Radich Andreas Hochhaus Tam ás Masszi Andrzej Hellmann Jesper Stentoft Mar ía Teresa Gómez Casares J. Valent ín García-Gutiérrez Eibhlin Conneally Philipp D. le Coutre Norbert Gattermann Bruno Martino Susanne Saussele Francis J. Giles Davi Source Type: research

Incidence of cardiovascular events in patients with chronic myeloid leukaemia treated with tyrosine kinase inhibitors
Acta Cardiol. 2021 Mar 8:1-6. doi: 10.1080/00015385.2021.1888017. Online ahead of print.ABSTRACTBACKGROUND: The introduction of imatinib and tyrosine kinase inhibitors as therapeutic strategy for Philadelphia chromosome-positive chronic myeloid leukaemia (CML) has represented an important step forward for treatment of this disease. The aim of this study was therefore to evaluate the incidence of cardiovascular adverse events (CVEs) in patients affected by CML treated with TKI in an observational prospective study.METHODS: All consecutive patients affected by CML and treated with TKI in our Institution were enrolled in the ...
Source: Acta Cardiologica - March 9, 2021 Category: Cardiology Authors: Grazia Casavecchia Giuseppina Spinosa Luisa De Gennaro Stefano Zicchino Matteo Gravina Michele Magnesa Matteo Di Biase Natale Daniele Brunetti Source Type: research

Quantification of eight hematological tyrosine kinase inhibitors in both plasma and whole blood by a validated LC-MS/MS method
Talanta. 2021 May 1;226:122140. doi: 10.1016/j.talanta.2021.122140. Epub 2021 Jan 28.ABSTRACTTherapeutic drug monitoring (TDM) of tyrosine kinase inhibitors (TKIs) in cancer therapy offers the potential to improve treatment efficacy while minimizing toxicity. Therefore, a high-throughput, sensitive LC-MS/MS method was developed and validated, to be used for personalized treatment of hematologic malignancies. The assay allows the simultaneous quantification in plasma (EDTA and heparin) and whole blood of eight TKIs, including bosutinib, dasatinib, gilteritinib, ibrutinib, imatinib, midostaurin, nilotinib and ponatinib, whic...
Source: Talanta - March 7, 2021 Category: Chemistry Authors: Nick Verougstraete Veronique Stove Alain G Verstraete Christophe Stove Source Type: research

Quantification of eight hematological tyrosine kinase inhibitors in both plasma and whole blood by a validated LC-MS/MS method
Talanta. 2021 May 1;226:122140. doi: 10.1016/j.talanta.2021.122140. Epub 2021 Jan 28.ABSTRACTTherapeutic drug monitoring (TDM) of tyrosine kinase inhibitors (TKIs) in cancer therapy offers the potential to improve treatment efficacy while minimizing toxicity. Therefore, a high-throughput, sensitive LC-MS/MS method was developed and validated, to be used for personalized treatment of hematologic malignancies. The assay allows the simultaneous quantification in plasma (EDTA and heparin) and whole blood of eight TKIs, including bosutinib, dasatinib, gilteritinib, ibrutinib, imatinib, midostaurin, nilotinib and ponatinib, whic...
Source: Talanta - March 7, 2021 Category: Chemistry Authors: Nick Verougstraete Veronique Stove Alain G Verstraete Christophe Stove Source Type: research

Quantification of eight hematological tyrosine kinase inhibitors in both plasma and whole blood by a validated LC-MS/MS method
Talanta. 2021 May 1;226:122140. doi: 10.1016/j.talanta.2021.122140. Epub 2021 Jan 28.ABSTRACTTherapeutic drug monitoring (TDM) of tyrosine kinase inhibitors (TKIs) in cancer therapy offers the potential to improve treatment efficacy while minimizing toxicity. Therefore, a high-throughput, sensitive LC-MS/MS method was developed and validated, to be used for personalized treatment of hematologic malignancies. The assay allows the simultaneous quantification in plasma (EDTA and heparin) and whole blood of eight TKIs, including bosutinib, dasatinib, gilteritinib, ibrutinib, imatinib, midostaurin, nilotinib and ponatinib, whic...
Source: Talanta - March 7, 2021 Category: Chemistry Authors: Nick Verougstraete Veronique Stove Alain G Verstraete Christophe Stove Source Type: research

Quantification of eight hematological tyrosine kinase inhibitors in both plasma and whole blood by a validated LC-MS/MS method
Talanta. 2021 May 1;226:122140. doi: 10.1016/j.talanta.2021.122140. Epub 2021 Jan 28.ABSTRACTTherapeutic drug monitoring (TDM) of tyrosine kinase inhibitors (TKIs) in cancer therapy offers the potential to improve treatment efficacy while minimizing toxicity. Therefore, a high-throughput, sensitive LC-MS/MS method was developed and validated, to be used for personalized treatment of hematologic malignancies. The assay allows the simultaneous quantification in plasma (EDTA and heparin) and whole blood of eight TKIs, including bosutinib, dasatinib, gilteritinib, ibrutinib, imatinib, midostaurin, nilotinib and ponatinib, whic...
Source: Talanta - March 7, 2021 Category: Chemistry Authors: Nick Verougstraete Veronique Stove Alain G Verstraete Christophe Stove Source Type: research

Real-life comparison of nilotinib versus dasatinib as second-line therapy in chronic phase chronic myeloid leukemia patients
AbstractTyrosine kinase inhibitors (TKIs), the backbone of treatment for chronic phase chronic myeloid leukemia patients (CP-CML), have changed the long-term outcome of the disease. Nonetheless, over 20% of patients fail front-line therapy due to intolerance or resistance. A head-to-head comparison of dasatinib and nilotinib as second-line treatment outside of sponsored clinical trials has not been reported. We retrospectively analyzed 131 CP-CML patients who, after front-line imatinib failure, switched to a second-line therapy with nilotinib (59, 45%) or dasatinib (72, 55%). Median duration of second-line treatment was 33...
Source: Annals of Hematology - March 7, 2021 Category: Hematology Source Type: research

Molecules, Vol. 26, Pages 1446: Structure-Based Virtual Screening Identifies Multiple Stable Binding Sites at the RecA Domains of SARS-CoV-2 Helicase Enzyme
id Muhammad With the emergence and global spread of the COVID-19 pandemic, the scientific community worldwide has focused on search for new therapeutic strategies against this disease. One such critical approach is targeting proteins such as helicases that regulate most of the SARS-CoV-2 RNA metabolism. The purpose of the current study was to predict a library of phytochemicals derived from diverse plant families with high binding affinity to SARS-CoV-2 helicase (Nsp13) enzyme. High throughput virtual screening of the Medicinal Plant Database for Drug Design (MPD3) database was performed on SARS-CoV-2 helicase using Au...
Source: Molecules - March 7, 2021 Category: Chemistry Authors: Sajjad Ahmad Yasir Waheed Saba Ismail Saadia Bhatti Sumra Wajid Abbasi Khalid Muhammad Tags: Article Source Type: research

Nilotinib restores memory function by preventing dopaminergic neuron degeneration in a mouse model of Alzheimer’s Disease
Publication date: Available online 5 March 2021Source: Progress in NeurobiologyAuthor(s): Livia La Barbera, Francescangelo Vedele, Annalisa Nobili, Paraskevi Krashia, Elena Spoleti, Emanuele Claudio Latagliata, Debora Cutuli, Emma Cauzzi, Ramona Marino, Maria Teresa Viscomi, Laura Petrosini, Stefano Puglisi-Allegra, Marcello Melone, Flavio Keller, Nicola Biagio Mercuri, Fiorenzo Conti, Marcello D’Amelio (Source: Progress in Neurobiology)
Source: Progress in Neurobiology - March 6, 2021 Category: Neuroscience Source Type: research

Discovery of a Novel CIP2A Variant (NOCIVA) with clinical relevance in predicting TKI resistance in myeloid leukemias
CONCLUSIONS: We discovered novel variant of the oncoprotein CIP2A and its clinical relevance in predicting tyrosine kinase inhibitor therapy resistance in myeloid leukemias.PMID:33674272 | DOI:10.1158/1078-0432.CCR-20-3679 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - March 6, 2021 Category: Cancer & Oncology Authors: Eleonora Makela Karolina Pavic Taru M Varila Urpu Salmenniemi Eliisa L öyttyniemi Srikar G Nagelli Tea Ammun ét Veli-Matti K ähäri Richard E Clark Laura L Elo Venkata Kumari Bachanaboyina Claire M Lucas Maija It älä-Remes Jukka Westermarck Source Type: research

Discovery of a Novel CIP2A Variant (NOCIVA) with clinical relevance in predicting TKI resistance in myeloid leukemias
CONCLUSIONS: We discovered novel variant of the oncoprotein CIP2A and its clinical relevance in predicting tyrosine kinase inhibitor therapy resistance in myeloid leukemias.PMID:33674272 | DOI:10.1158/1078-0432.CCR-20-3679 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - March 6, 2021 Category: Cancer & Oncology Authors: Eleonora Makela Karolina Pavic Taru M Varila Urpu Salmenniemi Eliisa L öyttyniemi Srikar G Nagelli Tea Ammun ét Veli-Matti K ähäri Richard E Clark Laura L Elo Venkata Kumari Bachanaboyina Claire M Lucas Maija It älä-Remes Jukka Westermarck Source Type: research

Discovery of a Novel CIP2A Variant (NOCIVA) with clinical relevance in predicting TKI resistance in myeloid leukemias
CONCLUSIONS: We discovered novel variant of the oncoprotein CIP2A and its clinical relevance in predicting tyrosine kinase inhibitor therapy resistance in myeloid leukemias.PMID:33674272 | DOI:10.1158/1078-0432.CCR-20-3679 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - March 6, 2021 Category: Cancer & Oncology Authors: Eleonora Makela Karolina Pavic Taru M Varila Urpu Salmenniemi Eliisa L öyttyniemi Srikar G Nagelli Tea Ammun ét Veli-Matti K ähäri Richard E Clark Laura L Elo Venkata Kumari Bachanaboyina Claire M Lucas Maija It älä-Remes Jukka Westermarck Source Type: research

Regulation of OATP1B1 function by tyrosine kinase-mediated phosphorylation
CONCLUSIONS: A novel kinase-dependent post-translational mechanism of OATP1B1 activation was identified and interference with this process by TKIs can influence the elimination of a broad range of xenobiotic substrates.PMID:33664059 | DOI:10.1158/1078-0432.CCR-21-0023 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - March 5, 2021 Category: Cancer & Oncology Authors: Elizabeth Hayden Mingqing Chen Kyle Z Pasquariello Alice A Gibson James J Petti Shichen Shen Jun Qu Su Sien Ong Taosheng Chen Yan Jin Muhammad Erfan Uddin Kevin M Huang Aviv Paz Alex Sparreboom Shuiying Hu Jason A Sprowl Source Type: research

Regulation of OATP1B1 function by tyrosine kinase-mediated phosphorylation
CONCLUSIONS: A novel kinase-dependent post-translational mechanism of OATP1B1 activation was identified and interference with this process by TKIs can influence the elimination of a broad range of xenobiotic substrates.PMID:33664059 | DOI:10.1158/1078-0432.CCR-21-0023 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - March 5, 2021 Category: Cancer & Oncology Authors: Elizabeth Hayden Mingqing Chen Kyle Z Pasquariello Alice A Gibson James J Petti Shichen Shen Jun Qu Su Sien Ong Taosheng Chen Yan Jin Muhammad Erfan Uddin Kevin M Huang Aviv Paz Alex Sparreboom Shuiying Hu Jason A Sprowl Source Type: research

Adverse events associated with nilotinib in chronic myeloid leukaemia: mechanisms and management strategies
Expert Rev Clin Pharmacol. 2021 Feb 23. doi: 10.1080/17512433.2021.1894129. Online ahead of print.ABSTRACTINTRODUCTION: Nilotinib is a second-generation tyrosine kinase inhibitor (TKI) targeting BCR/ABL, which is used for the first-line treatment of newly-diagnosed chronic myeloid leukemia (CML) patients and the second-line treatment of most CML patients who are resistant or intolerant to prior therapy that includes imatinib. In addition to common adverse reactions, long-term use of nilotinib shows some toxicities that are different from those of occurring during other BCR/ABL TKI treatment, such as cardiovascular toxicity...
Source: Expert Review of Clinical Pharmacology - February 23, 2021 Category: Drugs & Pharmacology Authors: Zeng Wang Liyu Jiang Hao Yan Zhifei Xu Peihua Luo Source Type: research

Adverse events associated with nilotinib in chronic myeloid leukemia: mechanisms and management strategies
Expert Rev Clin Pharmacol. 2021 Feb 28:1-12. doi: 10.1080/17512433.2021.1894129. Online ahead of print.ABSTRACTIntroduction: Nilotinib is a second-generation tyrosine kinase inhibitor (TKI) targeting BCR/ABL, which is used for the first-line treatment of newly diagnosed chronic myeloid leukemia (CML) patients and the second-line treatment of most CML patients who are resistant or intolerant to prior therapy that includes imatinib. In addition to common adverse reactions, long-term use of nilotinib shows some toxicities that are different from those of occurring during other BCR/ABL TKI treatments, such as cardiovascular to...
Source: Expert Review of Clinical Pharmacology - February 23, 2021 Category: Drugs & Pharmacology Authors: Zeng Wang Liyu Jiang Hao Yan Zhifei Xu Peihua Luo Source Type: research