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Tyrosine kinase inhibitors

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https://www.readbyqxmd.com/read/29782975/roles-of-germline-jak2-activation-mutation-jak2-v625f-in-the-pathology-of-myeloproliferative-neoplasms
#1
Qing-Yun Wu, Meng-Meng Ma, Lin Fu, Yuan-Yuan Zhu, Yang Liu, Jiang Cao, Ping Zhou, Zhen-Yu Li, Ling-Yu Zeng, Feng Li, Xiao-Yun Wang, Kai-Lin Xu
Janus tyrosine kinase 2 (JAK2) mediates downstream signaling of cytokine receptors in all hematological lineages, constitutively active somatic JAK2 mutations play key roles in the pathology of myeloproliferative neoplasms (MPNs). Recently, germline JAK2 mutations are also associated with triple-negative MPNs. A novel germline mutation JAK2 V625F is reported to be involved in a subset of MPNs patients. However, the pathogenesis of this mutation caused MPN is still unclear. In this study, the homology models of JAK2 V625F showed that the newly formed interaction between F625 and Y613 disrupted the JAK2 JH1-JH2 domain interactions was responsible for its activation, when F625 and Y613 interaction was disrupted, its activity significantly decreased...
May 18, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29782564/stressing-the-need-to-overcome-egfr-tyrosine-kinase-inhibitor-resistance
#2
EDITORIAL
Leila Toulabi, Bríd M Ryan
No abstract text is available yet for this article.
April 2018: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/29782303/clindamycin-induced-maculopapular-exanthema-with-preferential-involvement-of-striae-distensae-a-koebner-phenomenon
#3
Benigno Monteagudo, Miguel Cabanillas, Pilar Iriarte, Aquilina Ramírez-Santos, Elvira León-Muinos, Daniel González-Vilas, Óscar Suárez-Amor
Clindamycin is a lincomycin-derived antibiotic useful for the treatment of anaerobic and Gram-positive aerobic bacterial infections. Cutaneous adverse reactions are usually maculopapular exanthemas, although hypersensitivity syndrome, acute generalized exanthematous pustulosis, and Stevens-Johnson syndrome have also been reported (1). We report the case of a patient with a maculopapular rash triggered by clindamycin who developed cutaneous lesions on striae distensae (SD). A 47-year-old woman was referred to our clinic for pruritic cutaneous lesions which had started 6 days earlier...
April 2018: Acta Dermatovenerologica Croatica: ADC
https://www.readbyqxmd.com/read/29781323/targeting-the-b-cell-receptor-pathway-a-review-of-current-and-future-therapies-for-non-hodgkin-s-lymphoma
#4
Thomas D Rodgers, Patrick M Reagan
The B-cell receptor (BCR) pathway is a crucial aspect of mature lymphocytes and is maintained in B-cell neoplasms. Many small module inhibitors targeting kinases within the BCR pathway are approved, with others in development, offering alternative treatment options to standard chemoimmunotherapy. Areas Covered: This review covers both approved inhibitors and investigational inhibitors of spleen tyrosine kinase (SYK), Bruton's tyrosine kinase (BTK), and phosphoinositide-3-kinase (PI3K) in the treatment of B-cell lymphomas...
May 20, 2018: Expert Opinion on Emerging Drugs
https://www.readbyqxmd.com/read/29781317/combination-therapies-for-the-treatment-of-her2-positive-breast-cancer-current-and-future-prospects
#5
Mariana Brandão, Noam F Pondé, Francesca Poggio, Nuria Kotecki, Mauren Salis, Matteo Lambertini, Evandro de Azambuja
HER2-positive disease is an aggressive subtype of breast cancer that has been revolutionized by anti-HER2 directed therapies. Multiple drugs have been developed and are currently in clinical use, including trastuzumab, lapatinib, pertuzumab, T-DM1 and neratinib, alone or combined in "dual HER2-blockade" regimens. Areas covered: A comprehensive literature review was performed regarding the current state and the future of combination regimens containing anti-HER2 agents, focusing on their efficacy, toxicity and cost-effectiveness...
May 21, 2018: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/29780937/vogt-koyanagi-harada-disease-like-presentation-in-patients-with-chronic-myeloid-leukemia
#6
Saurabh Mistry, S Sudharshan, Suganeswari Ganesan, Ashraf Banu Akbar, Jyotirmay Biswas
Purpose: To report two rare cases of chronic myeloid leukemia (CML) on tyrosine kinase inhibitors presenting as bilateral serous retinal detachment and ocular inflammation, simulating Vogt-Koyanagi-Harada (VKH) disease. Methods: Case series and review of literature. Result: Two young patients (one male and one female) with CML on treatment with tyrosine kinase inhibitors (imatinib and dasatanib) under remission presented with bilateral sudden vision loss...
June 2018: American Journal of Ophthalmology Case Reports
https://www.readbyqxmd.com/read/29780814/targeting-chronic-myeloid-leukemia-stem-cells-can-transcriptional-program-be-a-druggable-target-for-cancers
#7
REVIEW
Yosuke Masamoto, Mineo Kurokawa
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm resulting from acquisition of constitutively active BCR-ABL protein tyrosine kinase in a hematopoietic stem cell (HSC). Though tyrosine kinase inhibitors (TKIs) have changed a fatal disease into manageable disease, most patients cannot discontinue TKI treatment due to persistence of TKI-resistant leukemia stem cells (LSCs). Much effort has been made to find out factors or pathways specifically operating in LSCs to selectively target LSCs, with some promising results at least in preclinical models...
2018: Stem Cell Investigation
https://www.readbyqxmd.com/read/29777941/characterization-of-the-binding-of-a-novel-antitumor-drug-ibrutinib-with-human-serum-albumin-insights-from-spectroscopic-calorimetric-and-docking-studies
#8
Bin Tang, Peixiao Tang, Jiawei He, Hongqin Yang, Hui Li
Ibrutinib (IBR) is a novel Bruton's tyrosine kinase inhibitor and shows good efficacy for several B-cell malignancies. In the current study, the molecular mechanism of the interaction between IBR and the transport protein human serum albumin (HSA) was ascertained by spectroscopic, calorimetric, and docking studies. Detailed investigations on affinity parameter, binding model, conformational change, and site selectivity were implemented by receptor-based and ligand-based analysis. An unusual fluorescence co-quenching (mutual quenching) was observed in the binding of IBR to HSA, followed by a static mechanism...
May 16, 2018: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/29777599/immense-random-colocalization-revealed-by-automated-high-content-image-cytometry-seriously-questions-fish-as-gold-standard-for-detecting-eml4-alk-fusion
#9
Gábor Smuk, Tamás Tornóczky, László Pajor, Ilse Chudoba, Béla Kajtár, Veronika Sárosi, Gábor Pajor
EML4-ALK gene fusion (inv2(p21p23)) of non-small cell lung cancer (NSCLC) predisposes to tyrosine kinase inhibitor treatment. One of the gold standard diagnostics is the dual color (DC) break-apart (BA) FISH technique, however, the unusual closeness of the involved genes has been suggested to raise likelihood of random co-localization (RCL) of signals. Although this is suspected to decrease sensitivity (often to as low as 40-70%), the exact level and effect of RCL has not been revealed thus far. Signal distances were analyzed to the 0...
May 19, 2018: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
https://www.readbyqxmd.com/read/29776413/the-cxcr4-antagonist-plerixafor-amd3100-promotes-proliferation-of-ewing-sarcoma-cell-lines-in-vitro-and-activates-receptor-tyrosine-kinase-signaling
#10
Philipp Berning, Christiane Schaefer, Dagmar Clemens, Eberhard Korsching, Uta Dirksen, Jenny Potratz
BACKGROUND: The CXCR4 receptor antagonist plerixafor (AMD3100) is raising interest as an anti-cancer agent that disrupts the CXCL12-CXCR4 chemokine - receptor interaction between neoplastic cells and their microenvironment in tumor progression and metastasis. Here, we investigated plerixafor for anti-cancer activity in Ewing sarcoma, a rare and aggressive cancer of bone and soft tissues. METHODS: We used a variety of methods such as cell viability and migration assays, flow cytometry, phospho-tyrosine arrays and western blotting to determine plerixafor effects on five characterized Ewing sarcoma cell lines and a low-passage culture in vitro...
May 18, 2018: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29775809/transient-asymptomatic-pulmonary-opacities-during-osimertinib-treatment-and-its-clinical-implication
#11
Hansang Lee, Ho Yun Lee, Jong-Mu Sun, Se-Hoon Lee, Youjin Kim, Song Ee Park, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn
INTRODUCTION: Osimertinib is an oral, potent, irreversible 3rd generation EGFR tyrosine kinase inhibitor (TKI) approved for the treatment of T790M positive non-small cell lung cancer (NSCLC) patients who failed 1st or 2nd generation EGFR TKIs. Interstitial lung disease (ILD) is a rare complication with osimertinib, occurring in 1-3%. Recently, relatively high incidence of transient asymptomatic pulmonary opacities (TAPOs) which are different from ILD has been described. However, its clinical implication has not been fully determined yet...
May 15, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29774795/prospective-evaluation-of-hypogonadism-in-male-metastatic-renal-cell-carcinoma-patients-treated-with-targeted-therapies
#12
Julie Bastin, Emilie Werbrouck, Annelies Verbiest, Kevin Punie, Oliver Bechter, Sherida Feng Woei-A-Jin, Pascal Wolter, Hans Wildiers, Evelyne Lerut, Herlinde Dumez, Brigitte Decallonne, Paul Clement, Dirk Vanderschueren, Maarten Albersen, Raymond Oyen, Patrick Schöffski, Benoit Beuselinck
Objectives To study the prevalence of hypogonadism in male patients with metastatic renal cell carcinoma (mRCC) starting with targeted therapies and the impact of the vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) sunitinib and pazopanib on the luteinizing hormone (LH)/testosterone (TT)-axis. Methods Male mRCC patients starting with targeted therapies were prospectively included in this study. TT- and LH-levels were sampled at start as well as during systemic therapy. Endpoints of the study were gonadal status (TT- and LH-levels) at start of targeted therapy and TT- and LH-evolution during targeted therapy...
May 18, 2018: Acta Clinica Belgica
https://www.readbyqxmd.com/read/29774782/the-neuroprotective-effect-of-ethanol-intoxication-in-tbi-is-associated-with-the-suppression-of-erbb-signaling-in-pv-positive-interneurons
#13
Akila Chandrasekar, Florian Olde Heuvel, Martin Wepler, Rida Rehman, Annette Palmer, Alberto Catanese, Birgit Linkus, Albert Ludolph, Tobias Boeckers, Markus Huber-Lang, Peter Radermacher, Francesco Roselli
Ethanol intoxication (EI) is a frequent comorbidity of TBI, but the impact of EI on TBI pathogenic cascades and prognosis is unclear: although clinical evidence suggests that EI may have neuroprotective effects, experimental support is, to date, inconclusive. We aimed at elucidating the impact of EI on TBI-associated neurological deficits, signaling pathways and pathogenic cascades, in order to identify new modifiers of TBI pathophysiology. We have shown that ethanol administration (5g/Kg) before trauma enhances behavioral recovery in a weight-drop TBI model; neuronal survival in the injured somatosensory cortex was enhanced by EI...
May 18, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29774100/differential-proteomic-profile-of-leukemic-cd34-progenitor-cells-from-chronic-myeloid-leukemia-patients
#14
Maria Rosaria Ricciardi, Valentina Salvestrini, Roberto Licchetta, Simone Mirabilii, Mattia Forcato, Gabriele Gugliotta, Simona Salati, Fausto Castagnetti, Gianantonio Rosti, Massimo Breccia, Giuliana Alimena, Rossella Manfredini, Silvio Bicciato, Roberto Massimo Lemoli, Agostino Tafuri
Chronic Myeloid Leukemia (CML) is a stem cell disease sustained by a rare population of quiescent cells which are to some extent resistant to tyrosine kinase inhibitors (TKIs). BCR-ABL oncogene activates multiple cross-talking signal transduction pathways (STP), such as RAS/MEK/ERK, PI3K/Akt, Wnt and STAT5, contributing to abnormal proliferation of clonal cells. From this perspective, the aim of this study was to analyze the expression and activation profile of STP involved in the mechanisms of cell proliferation/quiescence and survival of the progenitor CD34+ cells from chronic phase (CP) CML...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774061/immunotherapy-in-non-metastatic-non-small-cell-lung-cancer-can-the-benefits-of-stage-iv-therapy-be-translated-into-earlier-stages
#15
REVIEW
Griet Deslypere, Dorothée Gullentops, Els Wauters, Johan Vansteenkiste
Over the last decade, several steps forward in the treatment of patients with stage IV non-small cell lung cancer (NCSLC) were made. Examples are the use of pemetrexed, pemetrexed maintenance therapy, or bevacizumab for patients with nonsquamous NSCLC. A big leap forward was the use of tyrosine kinase inhibitors in patients selected on the basis of an activating oncogene, such as epidermal growth factor receptor ( EGFR ) activating mutations or anaplastic lymphoma kinase ( ALK ) translocations. However, all of these achievements could not be translated into survival benefits when studied in randomized controlled trials in patients with nonmetastatic NSCLC...
2018: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/29774010/efficacy-of-vandetanib-in-treating-locally-advanced-or-metastatic-medullary-thyroid-carcinoma-according-to-recist-criteria-a-systematic-review-and-meta-analysis
#16
Pierpaolo Trimboli, Marco Castellana, Camilla Virili, Francesco Giorgino, Luca Giovanella
Background: Vandetanib is the most largely used tyrosine kinase inhibitor (TKI) in patients with locally advanced and/or metastatic medullary thyroid cancer (MTC). Here, we conducted a systematic review on its efficacy and attempted to perform a meta-analysis adopting standardized RECIST criteria as end-points. Methods: The terms "medullary thyroid" and "protein kinase inhibitor" (then including all TKIs) were searched in PubMed, ClinicalTrials...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29773593/safety-and-efficacy-of-second-line-bosutinib-for-chronic-phase-chronic-myeloid-leukemia-over-a-five-year-period-final-results-of-a-phase-1-2-study
#17
Carlo Gambacorti-Passerini, Jorge E Cortes, Jeff H Lipton, Hagop M Kantarjian, Dong-Wook Kim, Philippe Schafhausen, Rocco Crescenzo, Nathalie Bardy-Bouxin, Mark Shapiro, Kay Noonan, Eric Leip, Liza DeAnnuntis, Tim H Brümmendorf, H Jean Khoury
Bosutinib is a Src/Abl tyrosine kinase inhibitor indicated for adults with newly-diagnosed Ph+ chronic myeloid leukemia or with resistant/intolerant disease. We report the final results of a phase 1/2 study of second-line bosutinib in chronic phase chronic myeloid leukemia patients after imatinib failure (n=284). Median follow-up and treatment durations were 54.8 (range, 0.6-96.3) and 25.6 (0.2&-96.3) months, respectively. At years 2 and 5, 54% and 40% of patients, respectively, remained on bosutinib. Cumulative major cytogenetic response and complete cytogenetic response rates (newly-attained or maintained from baseline) were 58% and 46%, respectively, by year 2 and 60% and 50% by year 5...
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29773493/normalization-of-c-reactive-protein-levels-following-cytoreductive-nephrectomy-in-patients-with-metastatic-renal-cell-carcinoma-treated-with-tyrosine-kinase-inhibitors-is-associated-with-improved-overall-survival
#18
Jun Teishima, Shinya Ohara, Shunsuke Shinmei, Shogo Inoue, Tetsutaro Hayashi, Hideki Mochizuki, Koji Mita, Masanobu Shigeta, Akio Matsubara
INTRODUCTION AND OBJECTIVES: Pretreated C-reactive protein (CRP) has been suggested as one of the most important prognostic factors for metastatic renal cell carcinoma (mRCC). The aim of this study was to investigate the prognostic impact of the change in CRP level before and after cytoreductive nephrectomy (CN) in patients with mRCC treated with tyrosine kinase inhibitor. MATERIALS AND METHODS: The CRP in 60 patients undergoing molecular targeted therapy for mRCC was measured before and after CN...
May 14, 2018: Urologic Oncology
https://www.readbyqxmd.com/read/29773429/real-life-experience-with-ponatinib-in-chronic-myeloid-leukemia-a-multicenter-observational-study
#19
Adi Shacham-Abulafia, Pia Raanani, David Lavie, Yulia Volchek, Ron Ram, Ilana Helman, Liat Shargian, Anna Gourevitch, Evgeni Chubar, Roy Ratzon, Uri Rozovski
BACKGROUND: The strict recruitment criteria of patients for clinical trials often lead to reduced generalizability of the findings. We studied how ponatinib is used outside clinical trials in patients with chronic myeloid leukemia (CML). PATIENTS AND METHODS: The present retrospective study included all patients with a diagnosis of CML who had received ponatinib in 7 medical centers in Israel. RESULTS: From 2011 to 2016, we identified 37 patients with CML who had received ponatinib, 21 in the chronic phase and 16 in the advanced phase...
May 7, 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29772459/tyrosine-kinase-inhibitors-for-brain-metastases-in-her2-positive-breast-cancer
#20
REVIEW
Renata Duchnowska, Sibylle Loibl, Jacek Jassem
Approximately 30-50% of advanced HER2-positive breast cancer patients will develop central nervous system (CNS) metastases, with an annual risk of around 10%, and a half of them will die from brain progression. An increased risk of brain metastases is also seen in patients with early HER2-positive breast cancer administered curative therapy. Brain metastases in HER2-positive breast cancer patients usually constitute the first site of recurrence. The administration of anti-HER2 monoclonal antibodies, trastuzumab and pertuzumab, considerably delays the onset of symptomatic brain disease: however, the limited penetration of these compounds into the CNS hinders their efficacy...
May 9, 2018: Cancer Treatment Reviews
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