Cancers, Vol. 12, Pages 826: Cardiovascular Toxicity of Tyrosine Kinase Inhibitors Used in Chronic Myeloid Leukemia: An Analysis of the FDA Adverse Event Reporting System Database (FAERS)
sco Salvo Tyrosine kinase inhibitors (TKIs), the treatment of choice for chronic myeloid leukemia (CML), can be associated to cardiovascular (CV) adverse events (AEs). A case/non-case study was performed using AE reports registered in the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database to compare the risk of CV event reports related to TKIs indicated in the management of chronic myeloid leukemia (CML). Disproportionality of CV event-related TKIs was computed using the Reporting Odds Ratio (ROR) as a measure of potential risk increase. Nilotinib accounts for more than half of reported ...
Source: Cancers - March 30, 2020 Category: Cancer & Oncology Authors: Santa Cirmi Asmae El Abd Louis Letinier Michele Navarra Francesco Salvo Tags: Article Source Type: research

Molecules, Vol. 25, Pages 1571: Lapatinib, Nilotinib and Lomitapide Inhibit Haemozoin Formation in Malaria Parasites
This study presents a comparison of different in silico methods to identify new haemozoin-inhibiting chemotherapeutic alternatives for malaria that proved to be useful in different ways when taking into consideration their strengths and limitations. (Source: Molecules)
Source: Molecules - March 29, 2020 Category: Chemistry Authors: Ana Carolina C. de de Sousa Keletso Maepa Jill M. Combrinck Timothy J. Egan Tags: Article Source Type: research

Hepatitis B flare during osimertinib targeted therapy in a lung cancer patient with a resolved hepatitis B virus infection
Chronic Hepatitis B Virus (HBV) infection is concerning public health issue worldwide. Acute HBV reactivation may occur and cause the development of fulminant hepatitis flare, hepatic failure, and death. Cytotoxic chemotherapy has been known to be a risk factor for HBV reactivation, in which 20 –50% of patients may suffer from abrupt hepatitis flare [1]. In addition to chemotherapy, Tyrosine Kinase Inhibitors (TKIs), such as BCR–ABL TKI Imatinib and nilotinib, are also reported to be risk factors surrounding HBV reactivation [2]; therefore, TKI has been categorised and placed into a cl ass of moderate risk of r...
Source: European Journal of Cancer - March 20, 2020 Category: Cancer & Oncology Authors: Po-Hsin Lee, Teng-Yu Lee, Gee-Chen Chang Tags: Letter to the Editor Source Type: research

Pharmacokinetics of dasatinib in a hemodialysis patient with chronic myeloid leukemia and chronic kidney disease.
Abstract Until now, no studies have addressed the use of dasatinib in hemodialysis patients. Herein, we report the case of a 73-year-old hemodialysis patient with chronic myeloid leukemia (CML) who was treated with dasatinib. For 5 years prior, the patient had received nilotinib for the treatment of CML. Regular hemodialysis was initiated due to progression of hypertensive nephrosclerosis, whereupon nilotinib was discontinued and the patient began receiving 100 mg dose of dasatinib once daily. On dialysis days, dasatinib was administered immediately after completion of dialysis. Four months after startin...
Source: International Journal of Hematology - March 9, 2020 Category: Hematology Authors: Mori J, Oshima K, Tanimoto T, Ishizuka H, Kimura S, Miura M, Takahashi N Tags: Int J Hematol Source Type: research

Treatment outcomes of chronic-phase chronic myeloid leukemia with resistance and/or intolerance to a 1st-line tyrosine kinase inhibitor in Japan: the results of the New TARGET study 2nd-line.
This study demonstrated that CML-CP patients in Japan who are resistant and/or intolerant to a 1st-line TKI can achieve an extremely good outcome by 2nd-line TKI treatment. PMID: 32152876 [PubMed - as supplied by publisher] (Source: International Journal of Hematology)
Source: International Journal of Hematology - March 9, 2020 Category: Hematology Authors: Sakurai M, Okamoto S, Matsumura I, Murakami S, Takizawa M, Waki M, Hirano D, Watanabe-Nakaseko R, Kobayashi N, Iino M, Mitsui H, Ishikawa Y, Takahashi N, Kawaguchi T, Suzuki R, Yamamoto K, Kizaki M, Ohnishi K, Naoe T, Akashi K, New TARGET investigators Tags: Int J Hematol Source Type: research

Targeting BCL-2 as a Therapeutic Strategy for Primary p210BCR-ABL1-positive B-ALL Cells
Conclusion: BCL-2 is a key survival factor for primary Ph+ B-ALL cells and its inhibition - alone or in combination with a BCR-ABL1 TKI - should be further investigated as a potential therapeutic strategy for these patients. (Source: In Vivo)
Source: In Vivo - February 28, 2020 Category: Research Authors: MASSIMINO, M., TIRRO, E., STELLA, S., PENNISI, M. S., VITALE, S. R., PUMA, A., ROMANO, C., DI GREGORIO, S., ROMEO, M. A., DI RAIMONDO, F., MANZELLA, L. Tags: Experimental Studies Source Type: research

Preparation and optimization of nilotinib self-micro emulsifying drug delivery systems to enhance oral bioavailability.
Conclusion: This research demonstrated that SMEDDS could be an effective approach to improve solubility and oral bioavailability for the BCS class II poorly soluble nilotinib. PMID: 32067499 [PubMed - as supplied by publisher] (Source: Drug Development and Industrial Pharmacy)
Source: Drug Development and Industrial Pharmacy - February 19, 2020 Category: Drugs & Pharmacology Tags: Drug Dev Ind Pharm Source Type: research

Role of Platelet-Derived Growth Factor (PDGF) in Asthma as an Immunoregulatory Factor Mediating Airway Remodeling and Possible Pharmacological Target
Asthma is a chronic and heterogenic disease of the respiratory system, one of the most common lung diseases worldwide. The underlying pathologies, which are chronic inflammatory process and airway remodeling (AR), are mediated by numerous cells and cytokines. Particularly interesting in this field is the platelet-derived growth factor (PDGF), one of the members of the human growth factor family. In this article, the authors analyze the available data on the role of PDGF in asthma in experimental models and in human research. PDGF is expressed in airway by various cells contributing to asthma pathogenesis—mast cells, ...
Source: Frontiers in Pharmacology - February 14, 2020 Category: Drugs & Pharmacology Source Type: research

The Role of Donor Lymphocyte Infusion (DLI) in Post Hematopoietic Cell Transplant (HCT) Relapse for Chronic Myeloid Leukemia (CML) in the Tyrosine Kinase Inhibitor (TKI) Era
The optimal approach to patients with chronic myeloid leukemia (CML) that relapse following allogeneic hematopoietic cell transplantation (HCT) in the tyrosine kinase inhibitors (TKIs) era is unknown. Imatinib was introduced in 2001 being followed by the introduction of second generation TKIs such as dasatinib or nilotinib, in subsequent years [1,2]. In later years, the spectrum of TKIs has further broadened, given the introduction of bosutinib and ponatinib [3,4]. Nevertheless, allogeneic HCT remains an important rescue strategy for some CML patients at adverse risk. (Source: Biology of Blood and Marrow Transplantation)
Source: Biology of Blood and Marrow Transplantation - February 13, 2020 Category: Hematology Authors: Sarah Schmidt, Ying Liu, Zhen-Huan Hu, Kirsten M. Williams, Hillard M. Lazarus, Ravi Vij, Mohamed A. Kharfan-Dabaja, Guillermo Ort í, Peter H. Wiernik, Daniel Weisdorf, Rammurti T. Kamble, Roger Herzig, Baldeep Wirk, Jan Cerny, Ulrike Bacher, Naeem A Cha Source Type: research

The Role of Donor Lymphocyte Infusion (DLI) in Post-Hematopoietic Cell Transplant (HCT) Relapse for Chronic Myeloid Leukemia (CML) in the Tyrosine Kinase Inhibitor (TKI) Era
The optimal approach to patients with chronic myeloid leukemia (CML) who relapse following allogeneic hematopoietic cell transplantation (HCT) in the tyrosine kinase inhibitor (TKI) era is unknown. Imatinib was introduced in 2001, followed by the introduction of second-generation TKIs such as dasatinib or nilotinib in subsequent years [1,2]. In later years, the spectrum of TKIs has further broadened, given the introduction of bosutinib and ponatinib [3,4]. Nevertheless, allogeneic HCT remains an important rescue strategy for some patients with CML at adverse risk. (Source: Biology of Blood and Marrow Transplantation)
Source: Biology of Blood and Marrow Transplantation - February 13, 2020 Category: Hematology Authors: Sarah Schmidt, Ying Liu, Zhen-Huan Hu, Kirsten M. Williams, Hillard M. Lazarus, Ravi Vij, Mohamed A. Kharfan-Dabaja, Guillermo Ort í, Peter H. Wiernik, Daniel Weisdorf, Rammurti T. Kamble, Roger Herzig, Baldeep Wirk, Jan Cerny, Ulrike Bacher, Naeem A. Ch Source Type: research

Targeted therapies in melanoma beyond BRAF: targeting NRAS-mutated and KIT-mutated melanoma
Purpose of review Melanoma treatment have been revolutionized since 2010 by the development of immune checkpoint inhibitors, and, for BRAF-mutated melanoma, targeted therapies based on BRAF and MEK inhibitors, which is a model of effective targeted therapy in cancer. However, patients with BRAF wild type cannot benefit for such treatments. In this review, we will focus on the current clinical development of targeted therapies beyond BRAF, in NRAS-mutated and KIT-altered melanoma. Recent findings In NRAS-mutated melanoma, targeted therapies based on MEK inhibition are being developed as monotherapy or in combination wi...
Source: Current Opinion in Oncology - February 6, 2020 Category: Cancer & Oncology Tags: MELANOMA AND OTHER SKIN NEOPLASMS: Edited by Céleste Lebbe Source Type: research

Early diagnosis, clinical management, and follow-up of cardiovascular events with ponatinib
AbstractChronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by neoplastic transformation of pluripotent cells due to a typical cytogenetic and molecular mutation known as Philadelphia (Ph) chromosome. In 2001, the introduction of the tyrosine kinasis inhibitor (TKI) imatinib as a therapeutic strategy for CML with PH chromosome mutation represented an important step towards treatment of these patients, and nowadays, this drug represents the gold therapeutic standard in this clinical setting. A second generation of TKIs (dasatinib, nilotinib, and bosutinib) showed an effective action in all patients...
Source: Heart Failure Reviews - February 5, 2020 Category: Cardiology Source Type: research

Mechanistic perspective of protective effects of nilotinib against cisplatin-induced testicular injury in rats: role of JNK/caspase-3 signaling inhibition
In conclusion, nilotinib refinement of cisplatin induced testicular toxicity is attributed to enhancing antioxidant capabilities, decreasing apoptotic signals and restoring regenerative capacity of testes suggesting nilotinib to be used in conjunction with cisplatin in treatment protocols to avoid cisplatin induced long term testicular toxicity. (Source: Environmental Toxicology and Pharmacology)
Source: Environmental Toxicology and Pharmacology - February 4, 2020 Category: Environmental Health Source Type: research

Nilotinib
(Source: Reactions Weekly)
Source: Reactions Weekly - February 1, 2020 Category: Drugs & Pharmacology Source Type: research

Nilotinib treatment of patients affected by chronic graft-versus-host disease reduces collagen production and skin fibrosis by down-modulating the TGF- β and p-SMAD pathway.
Chronic Graft-Versus-Host Disease (cGVHD), a major complication of allogeneic stem cell transplantation (allo-HCT), is an immune-mediated disease resulting from a complex interaction between donor and recipient adaptive immunity, leading to reduced patient-reported quality of life and non-relapse mortality1,2. (Source: Biology of Blood and Marrow Transplantation)
Source: Biology of Blood and Marrow Transplantation - January 29, 2020 Category: Hematology Authors: Marinelli Busilacchi Elena, Costantini Andrea, Mancini Giorgia, Tossetta Giovanni, Olivieri Jacopo, Poloni Antonella, Viola Nadia, Butini Luca, Campanati Anna, Goteri Gaia, Marzioni Daniela, Attilio Olivieri Source Type: research

MicroRNA-141-5p Acts as a Tumor Suppressor via Targeting RAB32 in Chronic Myeloid Leukemia
MicroRNA-141-5p (miR-141-5p), an important member of the miR-200 family, has been reported to be involved in cellular proliferation, migration, invasion, and drug resistance in different kinds of human malignant tumors. However, the role and function of miR-141-5p in chronic myeloid leukemia (CML) are unclear. In this current study, we found that the level of miR-141-5p was significantly decreased in peripheral blood cells from CML patients compared with normal blood cells and human leukemic cell line (K562 cells) compared with normal CD34+ cells, but was remarkably elevated in patients after treatment with nilotinib or im...
Source: Frontiers in Pharmacology - January 22, 2020 Category: Drugs & Pharmacology Source Type: research

Magnetic molecularly imprinted electrospun nanofibers for selective extraction of nilotinib from human serum.
Abstract A new magnetic molecularly imprinted nanofiber (MMIN) nanocomposite was prepared and used to the selective extraction of nilotinib. MMIN was constructed using a novel and general method including a combination of molecular imprinting and electrospinning technology. By electrospun precursor nanofibers containing polyacrylonitrile, Fe3O4 magnetic nanoparticles, and nilotinib as the template, molecularly imprinted nanofibers were produced with a mean diameter of 500 nm and lengths up to several millimeters. The microstructure and morphology of the prepared MMIN were thoroughly investigated using techniq...
Source: Analytical and Bioanalytical Chemistry - January 21, 2020 Category: Chemistry Authors: Pirdadeh-Beiranvand M, Afkhami A, Madrakian T Tags: Anal Bioanal Chem Source Type: research

Feasibility Study of Switching to Nilotinib After First-line Imatinib in the Chronic Phase of Chronic Myeloid Leukemia
Publication date: Available online 9 December 2019Source: Clinical Lymphoma Myeloma and LeukemiaAuthor(s): Yilin Chen, Hua Yin, Lifeng Chen, Yingyuan Xiong, Li Meng, Jingming Guo, Haiyan Wang, Weiming LiAbstractBackgroundWe investigated the real-life choice of first-line treatment in the chronic phase of chronic myeloid leukemia (CML-CP) and the feasibility of switching to nilotinib after first-line imatinib.Patients and MethodsWe performed a retrospective analysis of the efficacy and safety of imatinib versus nilotinib as first-line therapy for patients with CML-CP. We also performed a comparative analysis of the efficacy...
Source: Clinical Lymphoma Myeloma and Leukemia - January 4, 2020 Category: Cancer & Oncology Source Type: research

Effect of dual inhibition of histone deacetylase and phosphatidylinositol-3 kinase in Philadelphia chromosome-positive leukemia cells
ConclusionTaken together, our results indicate that administration of CUDC-907, a dual PI3K and HDAC inhibitor, may be an effective strategy against ABL TKI-resistant cells, including cells harboring the T315I mutation. Moreover, CUDC-907 may enhance the cytotoxic effects of ABL TKI when a combined treatment strategy is used against Philadelphia chromosome-positive leukemia cells. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - January 4, 2020 Category: Cancer & Oncology Source Type: research

Nilotinib treatment induced large granular lymphocyte expansion and maintenance of longitudinal remission in a Philadelphia chromosome-positive acute lymphoblastic leukemia.
We report the case of a 65-year-old patient with Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) who showed LGLs expansion during nilotinib treatment. The patient achieved complete remission (CR) after multi-agent chemotherapy combined with dasatinib treatment. However, ALL relapsed in the central nervous system and bone marrow when treatment was interrupted due to interstitial pneumonia. Nilotinib treatment was subsequently started and the patient achieved second CR. Marked peripheral blood lymphocytosis emerged after the start of nilotinib treatment. CD8 + CD57 + cytot...
Source: International Journal of Hematology - January 1, 2020 Category: Hematology Authors: Hagihara M, Hua J, Inoue M, Uchida T, Ide S, Ohara S, Takaku T Tags: Int J Hematol Source Type: research

The link between interleukin-1 β and acute myocardial infarction in chronic myeloid leukemia patients treated with nilotinib: cross-sectional study
(Source: Annals of Hematology)
Source: Annals of Hematology - December 23, 2019 Category: Hematology Source Type: research

Standardization of BCR-ABL1 quantification on the International Scale in China using locally developed secondary reference panels
More than 95% of patients with chronic myeloid leukemia (CML) are characterized with Philadelphia chromosome (Ph) and the resultant BCR-ABL1 fusion gene (FG) [1]. Unique to the leukemic clone, the BCR-ABL1 FG transcripts could serve as both therapeutic and prognostic targets. Previous studies have demonstrated that the application of tyrosine kinase inhibitors (TKIs), such as imatinib, nilotinib, dasatinib, and bosutinib can achieve a major molecular response in a majority of the patients with Ph+ leukemia [2-7], and the detection of minimal residual disease (MRD) in patients with leukemia during treatment is an important ...
Source: Experimental Hematology - December 18, 2019 Category: Hematology Authors: Jia-wei Zhang, Yu Fu, Qi-sheng Wu, Li-hua Bao, Rong-xue Peng, Rui Zhang, Jin-ming Li Source Type: research

Nilotinib Effects on Safety, Tolerability, and Potential Biomarkers in Parkinson Disease
This randomized clinical trial evaluates the efficacy and safety of nilotinib hydrochloride for use in treatment of patients with Parkinson disease. (Source: JAMA Neurology)
Source: JAMA Neurology - December 16, 2019 Category: Neurology Source Type: research

Narrowing Path for Nilotinib and Other Potential Disease-Modifying Therapies for Parkinson Disease
Nilotinib hydrochloride, an Abelson tyrosine kinase inhibitor used in the treatment of chronic myeloid leukemia, has been in the neurology news since the results of the open-label, phase 1 study in a small group of patients with advanced Parkinson disease (PD) and dementia with Lewy bodies was reported at the Society for Neuroscience in Chicago in October 2015. The extensive media coverage that followed, supported by videos of nilotinib-treated participants getting up and walking from their wheelchairs, suggested that disease modification in PD was within reach with this drug. The corresponding publication documented that,...
Source: JAMA Neurology - December 16, 2019 Category: Neurology Source Type: research

Feasibility study on treatment of switching to nilotinib after first-line imatinib in the chronic phase of chronic myeloid leukemia
Publication date: Available online 9 December 2019Source: Clinical Lymphoma Myeloma and LeukemiaAuthor(s): Yilin Chen, Hua Yin, Lifeng Chen, Yingyuan Xiong, Li Meng, Jingming Guo, Haiyan Wang, Weiming LiAbstractTo investigate the real-life choice of first-line treatment in the chronic phase of chronic myeloid leukemia (CML-CP) and the feasibility of switching to nilotinib treatment strategy after first-line imatinib. We went through retrospective analysis of the efficacy and safety of imatinib versus nilotinib for first-line for CML-CP patients, and comparative analysis of the efficacy of sustained imatinib versus switchin...
Source: Clinical Lymphoma Myeloma and Leukemia - December 10, 2019 Category: Cancer & Oncology Source Type: research

Feasibility study on treatment of switching to nilotinib after first-line imatinib in the chronic phase of chronic myeloid leukemia
First-line imatinib can achieve similar efficacy as first-line nilotinib after standardized management according to the ELN recommendations. Treatment based on imatinib as first-line treatment, then switching to nilotinib after standardized management is feasible and effective. Both nilotinib and imatinib are well tolerated and safe. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - December 9, 2019 Category: Hematology Authors: Yilin Chen, Hua Yin, Lifeng Chen, Yingyuan Xiong, Li Meng, Jingming Guo, Haiyan Wang, Weiming Li Tags: Original Study Source Type: research

Feasibility Study of Switching to Nilotinib After First-line Imatinib in the Chronic Phase of Chronic Myeloid Leukemia
First-line imatinib can achieve efficacy similar to that with first-line nilotinib after standardized management in accordance with the European Leukemia Network recommendations. Treatment with imatinib as first-line treatment, with a switch to nilotinib after standardized management is feasible and effective. Both nilotinib and imatinib have been shown to be well tolerated and safe. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - December 9, 2019 Category: Hematology Authors: Yilin Chen, Hua Yin, Lifeng Chen, Yingyuan Xiong, Li Meng, Jingming Guo, Haiyan Wang, Weiming Li Tags: Original Study Source Type: research

Meeting the needs of CML patients in resource-poor countries.
Authors: Malhotra H, Radich J, Garcia-Gonzalez P Abstract Subsequent to the development and global availability of BCR/ABL-targeted tyrosine kinase inhibitors (TKIs), the prognosis of patients with chronic myeloid leukemia (CML), at least those in the chronic phase, has markedly improved, and in the developed world, the average lifespan of these patients is now close to that of age- and sex-matched subjects without the disease. However, the situation in low- and middle-income countries (LMICs) may not be so rosy. Many important differences in hematological cancers, including CML, have been highlighted in various pu...
Source: Hematology ASH Education Program - December 7, 2019 Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research

Utility of Therapeutic Drug Monitoring of Imatinib, Nilotinib, and Dasatinib in Chronic Myeloid Leukemia: A Systematic Review and Meta-analysis.
This study examined the utility of therapeutic drug monitoring (TDM) of imatinib, nilotinib, and dasatinib in adult patients with chronic-phase chronic myeloid leukemia (CML). TDM in CML entails the measurement of plasma tyrosine kinase inhibitor (TKI) concentration to predict efficacy and tolerability outcomes and to aid in clinical decision making. TDM was to be deemed useful if it could be used for predicting the effectiveness of a drug and/or the occurrence of adverse reactions. It was expected that the findings from the present study would allow for the definition of a therapeutic range of each TKI. METHODS: A sy...
Source: Clinical Therapeutics - December 4, 2019 Category: Drugs & Pharmacology Authors: García-Ferrer M, Wojnicz A, Mejía G, Koller D, Zubiaur P, Abad-Santos F Tags: Clin Ther Source Type: research

Clinically Approved Drugs Inhibit the Staphylococcus aureus Multidrug NorA Efflux Pump and Reduce Biofilm Formation
Staphylococcus aureus has acquired resistance to antibiotics since their first use. The S. aureus protein NorA, an efflux pump belonging to the major facilitator superfamily (MFS), contributes to resistance to fluoroquinolones (e.g., ciprofloxacin), biocides, dyes, quaternary ammonium compounds, and antiseptics. Different compounds have been identified as potential efflux pump inhibitors (EPIs) of NorA that result in increased intracellular concentration of antibiotics, restoring their antibacterial activity and cell susceptibility. However, none of the currently known EPIs have been approved for clinical use, probably due...
Source: Frontiers in Microbiology - December 3, 2019 Category: Microbiology Source Type: research

In silico drug repurposing for the identification of potential candidate molecules against arboviruses infection
Publication date: Available online 28 November 2019Source: Antiviral ResearchAuthor(s): Diana Montes-Grajales, Henry Puerta-Guardo, Diego A. Espinosa, Eva Harris, William Caicedo-Torres, Jesus Olivero-Verbel, Esperanza Martínez-RomeroAbstractArboviral diseases caused by dengue (DENV), Zika (ZIKV) and chikungunya (CHIKV) viruses represent a major public health problem worldwide, especially in tropical areas where millions of infections occur every year. The aim of this research was to identify candidate molecules for the treatment of these diseases among the drugs currently available in the market, through in silico ...
Source: Antiviral Therapy - November 30, 2019 Category: Virology Source Type: research

In silico drug repurposing for the identification of potential candidate molecules against arboviruses infection.
ero E Abstract Arboviral diseases caused by dengue (DENV), Zika (ZIKV) and chikungunya (CHIKV) viruses represent a major public health problem worldwide, especially in tropical areas where millions of infections occur every year. The aim of this research was to identify candidate molecules for the treatment of these diseases among the drugs currently available in the market, through in silico screening and subsequent in vitro evaluation with cell culture models of DENV and ZIKV infections. Numerous pharmaceutical compounds from antibiotics to chemotherapeutic agents presented high in silico binding affinity for th...
Source: Antiviral Research - November 28, 2019 Category: Virology Authors: Montes-Grajales D, Puerta-Guardo H, Espinosa DA, Harris E, Caicedo-Torres W, Olivero-Verbel J, Martínez-Romero E Tags: Antiviral Res Source Type: research

Towards a Personalized Treatment of Patients with Chronic Myeloid Leukemia
AbstractPurpose of ReviewTreatment goals and ambitions have even been upwardly revised since demonstration was made that under certain conditions, treatment-free remission was possible. Herein, we will discuss on how to try tailoring treatment choices to the unique characteristics of each patient.Recent FindingsSince the first-generation ATP-competitive TKI imatinib was made available in the clinic in 2001, second-generation drugs such as dasatinib, nilotinib and bosutinib and the third-generation TKI ponatinib have broadened the therapeutic armamentarium, providing effective salvage against intolerance and different types...
Source: Current Hematologic Malignancy Reports - November 23, 2019 Category: Hematology Source Type: research

Influence of gastrointestinal activity on the absorption of nilotinib.
Authors: Sasaki M, Aoyama T, Sugawara M, Takekuma Y Abstract Nilotinib has bioavailability (BA) of only about 25% or less. The purpose of this study was to evaluate the influence of gastrointestinal activity on the absorption of nilotinib. In order to change gastrointestinal activity, mosapride was used for enhancement and butylscopolamine was used for suppression. Experiments on oral administration of nilotinib using rats whose gastrointestinal activity was altered by mosapride or butylscopolamine were carried out. The results of oral administration of acetaminophen to rats with peristalsis movement changed showed...
Source: Drug Metabolism and Pharmacokinetics - November 19, 2019 Category: Drugs & Pharmacology Tags: Drug Metab Pharmacokinet Source Type: research

Planned Pregnancy in Female Patients with Chronic Myeloid Leukemia Receiving Tyrosine Kinase Inhibitor Therapy
Conclusion.Planned pregnancy might be pragmatic in female patients with CML on TKIs. Achieving deep molecular response and, importantly, MMR duration ≥3.5 years were significantly associated with maintaining MMR during pregnancy.Implications for Practice.Female patients with chronic myeloid leukemia on tyrosine kinase inhibitors (TKIs) wishing to conceive are currently advised to discontinue TKIs before conception. However, the ideal degree and duration of response before stopping TKI, in addition to whether there will be any adverse effect caused by a short exposure of TKI, is unknown. Data of 17 female patients, who a...
Source: The Oncologist - November 13, 2019 Category: Cancer & Oncology Authors: Xuelin Dou, Yazhen Qin, Xiaojun Huang, Qian Jiang Tags: Leukemias, Hematologic Malignancies Source Type: research

Varying effects of tyrosine kinase inhibitors on platelet function —A need for individualized CML treatment to minimize the risk for hemostatic and thrombotic complications?
In this study, we show that different TKIs used for treatment of Chronic Myeloid Leukemia have opposing effects on platelet function, with large inter ‐individual differences. Thus, in patients with high risk for hemostatic or thrombotic complications, we suggest that treatment with TKIs should be individualized to minimize risks associated with long‐term treatment. AbstractSince their introduction, tyrosine kinase inhibitors (TKIs, eg, imatinib, nilotinib, dasatinib, bosutinib, ponatinib) have revolutionized the treatment of chronic myeloid leukemia (CML). However, long ‐term treatment with TKIs is associated with s...
Source: Cancer Medicine - November 12, 2019 Category: Cancer & Oncology Authors: Suryyani Deb, Niklas Bokn äs, Clara Sjöström, Anjana Tharmakulanathan, Kourosh Lotfi, Sofia Ramström Tags: ORIGINAL RESEARCH Source Type: research

Role of RNF213 p.4810K variant in the development of intracranial arterial disease in patients treated with nilotinib
Nilotinib, a tyrosine kinase inhibitor, used for the treatment of chronic myeloid leukemia (CML), is known to produce atherosclerotic complications such as coronary artery disease, peripheral artery disease [1] and intracranial arterial stenosis/occlusion (ICASO) [2,3]. Middle cerebral artery (MCA) is the most common site involved in ICASO in CML patients treated with nilotinib [2]. It has been remained unknown what factors influence the development of ICASO in patients treated with nilotinib. Because reported patients with ICASO were rare, there is a possibility that some specific factors such as genetic mutations are ass...
Source: Journal of the Neurological Sciences - November 9, 2019 Category: Neurology Authors: Masahiro Uemura, Masato Kanazawa, Takuma Yamagishi, Takahiro Nagai, Mami Takahashi, Shingo Koide, Masayoshi Tada, Junsuke Shimbo, Aiko Isami, Kunihiko Makino, Masayoshi Masuko, Kouji Nikkuni, Kouichirou Okamoto, Shuichi Igarashi, Kenichi Morita, Osamu Ono Tags: Letter to the Editor Source Type: research

Variables associated with patient-reported symptoms in persons with chronic phase chronic myeloid leukemia receiving tyrosine kinase inhibitor therapy
Conclusions: Demographic and social variables, type of TKI-therapy, therapy duration, and depth of response were associated with patient-reported symptoms in persons with chronic phase CML. Certain symptoms have adverse impact on HRQoL. (Source: Medicine)
Source: Medicine - November 1, 2019 Category: Internal Medicine Tags: Research Article: Observational Study Source Type: research

Pharmacokinetics of nilotinib in pediatric patients with Philadelphia chromosome-positive chronic myeloid leukemia or acute lymphoblastic leukemia.
Abstract PURPOSE: We investigated nilotinib exposure in pediatric patients with chronic myeloid leukemia (CML) or Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) resistant to, relapsed on, refractory to, or intolerant of previous treatment. EXPERIMENTAL DESIGN: Fifteen patients (aged 1 to
Source: Clinical Cancer Research - November 1, 2019 Category: Cancer & Oncology Authors: Hijiya N, Zwaan CM, Rizzari C, Foa R, Abbink F, Lancaster D, Landman-Parker J, Millot F, Moppett J, Nelken B, Caterina Putti M, Tian X, Sinclair K, Santanastasio H, Buchbinder A, Kearns P Tags: Clin Cancer Res Source Type: research

Use of Droplet Digital Polymerase Chain Reaction for Detecting Minimal Residual Disease: A Prospective Multi-Institutional Study
Conclusion: We found that ddPCR is a sensitive method for detecting MRD and that MRD could affect the duration of the treatment response. (Source: In Vivo)
Source: In Vivo - October 29, 2019 Category: Research Authors: PARK, H., SHIN, D.-Y., KIM, I., SOHN, S.-K., KOH, Y., LEE, J.-H., LEE, K.-H., KIM, D.-Y., KIM, H.-J., AHN, J.-S., LEE, J.-O., BANG, S.-M., CHEONG, J.-W., PARK, S.-G., PARK, S., LEE, Y. J., AHN, S.-Y. Tags: Clinical Studies Source Type: research

Structure-based analysis and biological characterization of imatinib derivatives reveal insights towards the inhibition of wild-type BCR-ABL and its mutants.
Abstract To reveal insights into the inhibition of BCR-ABL and its mutants, structure-based computing methods, such as docking, molecular dynamics (MD) simulation, the molecular mechanics generalized born surface area (MMGBSA), and biological characterizations, were employed to analyze two main pharmacophore zones and two related regions of imatinib derivatives. The hydrophobic and halogen interactions formed by the trifluoromethyl, as well as T-shaped π-π interactions formed by the pyrimidine, were confirmed. For the imatinib derivatives, the impacts of the amide moiety (region A) and the pyridine (region B...
Source: Bioorganic and Medicinal Chemistry Letters - October 28, 2019 Category: Chemistry Authors: Yang M, Xi Q, Jia W, Wang X Tags: Bioorg Med Chem Lett Source Type: research

Long-Term Patterns of Oral Anticancer Agent Adoption, Duration, and Switching in Patients With CML.
CONCLUSIONS: A dramatic shift was seen in CML treatments away from traditional, nonoral chemotherapy toward use of novel oral TKIs between 2000 and 2017. As the costs of oral anticancer agents reach new highs, studies assessing the long-term health and financial outcomes among patients with CML are warranted. PMID: 31590146 [PubMed - in process] (Source: Journal of the National Comprehensive Cancer Network : JNCCN)
Source: Journal of the National Comprehensive Cancer Network : JNCCN - October 9, 2019 Category: Cancer & Oncology Tags: J Natl Compr Canc Netw Source Type: research

Nilotinib Ameliorates Folic Acid-Induced Acute Kidney Injury Through Modulation of TWEAK and HSP-70 Pathways.
CONCLUSION: Anti-inflammatory, anti-apoptotic and anti-oxidant potentials are the main mechanisms by which nilotinib can ameliorate folic acid-induced AKI. Modulation of TWEAK and HSP 70 pathways are thought to be the main contributor to the observed ameliorative potential. PMID: 31593741 [PubMed - as supplied by publisher] (Source: Toxicology)
Source: Toxicology - October 5, 2019 Category: Toxicology Authors: Zaghloul MS, Abdelrahman RS Tags: Toxicology Source Type: research

1094PUse of droplet digital polymerase chain reaction for detecting minimal residual disease: A prospective, multi-institutional study
ConclusionsWe found that ddPCR is a sensitive method for detecting MRD and that MRD could affect the duration of the treatment response.Legal entity responsible for the studyThe authors.FundingNovartis Pharmaceuticals Corporation.DisclosureAll authors have declared no conflicts of interest. (Source: Annals of Oncology)
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

Neuroprotective effect of nilotinib on pentylenetetrazol-induced epilepsy in adult rat hippocampus: involvement of oxidative stress, autophagy, inflammation, and apoptosis.
CONCLUSIONS: Nilotinib may have promising neuroprotective and antiepileptic effects against pentylenetetrazolinduced seizures through promoting the antioxidant, antifibrotic, anti-inflammatory, antiapoptotic pathways and inhibiting autophagy. PMID: 31556574 [PubMed - in process] (Source: Folia Neuropathologica)
Source: Folia Neuropathologica - September 28, 2019 Category: Pathology Authors: Attia GM, Elmansy RA, Elsaed WM Tags: Folia Neuropathol Source Type: research

Relapse Prevention with Tyrosine Kinase Inhibitors after Allogeneic Transplantation for Ph+ ALL, A Systematic Review
Relapse after stem cell transplantation for Philadelphia chromosome (Ph) positive acute lymphoblastic leukemia (ALL) remains a significant challenge. In this systematic review, we compare survival outcomes of second-generation tyrosine kinase inhibitors (TKIs) nilotinib and dasatinib with first generation imatinib when these agents are used after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Ph-positive ALL. In addition, we review the literature on TKI use to prevent relapse in patients who proceed to allo-HSCT beyond first complete response (>CR1). (Source: Biology of Blood and Marrow Transplantation)
Source: Biology of Blood and Marrow Transplantation - September 23, 2019 Category: Hematology Authors: Zabih Warraich, Pavan Tenneti, Theresa Thai, Anne Hubben, Hina Amin, Ali McBride, Sami Warraich, Abdul Hannan, Faiza Warraich, Navneet Majhail, Matt Kalaycio, Faiz Anwer Source Type: research

Relapse Prevention with Tyrosine Kinase Inhibitors after Allogeneic Transplantation for Philadelphia Chromosome –Positive Acute Lymphoblast Leukemia: A Systematic Review
Relapse after stem cell transplantation for Philadelphia chromosome –positive (Ph+) acute lymphoblastic leukemia (ALL) remains a significant challenge. In this systematic review, we compare survival outcomes of second-generation tyrosine kinase inhibitors (TKIs) nilotinib and dasatinib with first-generation TKI imatinib when these agents are used after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Ph+ ALL. In addition, we review the literature on TKI use to prevent relapse in patients who proceed to allo-HSCT beyond first complete response (>CR1). (Source: Biology of Blood and Marrow Transplantation)
Source: Biology of Blood and Marrow Transplantation - September 23, 2019 Category: Hematology Authors: Zabih Warraich, Pavan Tenneti, Theresa Thai, Anne Hubben, Hina Amin, Ali McBride, Sami Warraich, Abdul Hannan, Faiza Warraich, Navneet Majhail, Matt Kalaycio, Faiz Anwer Source Type: research

Cessation of nilotinib in patients with chronic myelogenous leukemia who have maintained deep molecular responses for 2 years: a multicenter phase 2 trial, stop nilotinib (NILSt).
Abstract The aim of this multicenter phase 2 trial, Stop Nilotinib (NILSt), was to examine the safety and efficacy of discontinuation of nilotinib in patients with chronic phase (CP)-chronic myelogenous leukemia (CML). Patients with CP-CML who had achieved molecular response (MR4.5) after initiation of imatinib or nilotinib therapy received consolidation therapy with nilotinib 300-400 mg twice daily for up to 24 months. Patients who maintained MR4.5 at 24 months of consolidation therapy proceeded to discontinuation of nilotinib. The study enrolled 149 patients; 112 patients proceeded to consolidatio...
Source: International Journal of Hematology - September 19, 2019 Category: Hematology Authors: Nagafuji K, Matsumura I, Shimose T, Kawaguchi T, Kuroda J, Nakamae H, Miyamoto T, Kadowaki N, Ishikawa J, Imamura Y, Yamazaki H, Akashi K, Kanakura Y Tags: Int J Hematol Source Type: research

Systematic Review and Meta-Analysis of -New-Generation Tyrosine Kinase Inhibitors versus Imatinib for Newly Diagnosed Chronic Myeloid Leukemia.
Abstract BACKGROUNDS: We performed this systematic review and meta-analysis to compare the efficacy of new-generation tyrosine kinase inhibitors (NG-TKIs; including dasatinib, nilotinib, bosutinib, radotinib, and ponatinib) versus imatinib for patients with newly diagnosed chronic myeloid leukemia (CML). SUMMARY: We identified randomized controlled trials comparing the efficacy of NG-TKIs versus imatinib as the first-line treatment for CML patients by searching the PubMed, Cochrane library, and EMBASE databases. Two reviewers independently extracted data and assessed study quality. A meta-analysis was perform...
Source: Acta Haematologica - September 12, 2019 Category: Hematology Authors: Pan P, Wang L, Wang Y, Shen L, Zheng P, Bi C, Zhang A, Lv Y, Xue Z, Sun M, Sun C, Li J, Jin L, Yao Y Tags: Acta Haematol Source Type: research

BCR-ABL1 tyrosine kinase inhibitor K0706 exhibits pre-clinical activity in Philadelphia chromosome-positive leukemia
Patients with chronic phase CML (CP-CML) are effectively managed with BCR-ABL1 tyrosine kinase inhibitors (TKIs) and their survival approaches that of age-matched controls [1]. K0706 was designed as a BCR-ABL1 TKI to provide an option for patients experiencing resistance or intolerance to the first-line TKIs imatinib, nilotinib, dasatinib, and bosutinib [2,3]. Structural elements that overlap with dasatinib and ponatinib are noted (Figure 1A). (Source: Experimental Hematology)
Source: Experimental Hematology - September 4, 2019 Category: Hematology Authors: Orlando Antelope, Nadeem Vellore, Anthony D. Pomicter, Ami B. Patel, Alexandria van Scoyk, Phillip M. Clair, Michael Deininger, Thomas O'Hare Tags: Brief Communication Source Type: research