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Qie He, Junfeng Zhu, David Dingli, Jasmine Foo, Kevin Zox Leder
Over the past decade, several targeted therapies (e.g. imatinib, dasatinib, nilotinib) have been developed to treat Chronic Myeloid Leukemia (CML). Despite an initial response to therapy, drug resistance remains a problem for some CML patients. Recent studies have shown that resistance mutations that preexist treatment can be detected in a substantial number of patients, and that this may be associated with eventual treatment failure. One proposed method to extend treatment efficacy is to use a combination of multiple targeted therapies...
October 2016: PLoS Computational Biology
Animesh Pardanani
: Disease overview:Systemic mastocytosis (SM) results from a clonal proliferation of abnormal mast cells (MC) in one or more extra-cutaneous organs. DIAGNOSIS: The major criterion is presence of multifocal clusters of morphologically abnormal MC in the bone marrow. Minor diagnostic criteria include elevated serum tryptase level, abnormal MC expression of CD25 and/or CD2, and presence of KITD816V. Risk stratification: The 2008 World Health Organization (WHO) classification of SM has been shown to be prognostically relevant...
November 2016: American Journal of Hematology
Surjit Singh, Pramod Kumar Sharma
Here, we present a case of chronic myeloid leukemia for which imatinib therapy was initated. Triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone was normal, and thyroid microsomal autoantibodies (TMA) were positive and patient was diagnosed as thyroiditis treated with corticosteroids for 1½ months which lead to resolution.
July 2016: Indian Journal of Pharmacology
Achim Paulmichl, Dominik Summer, Claudia Manzl, Christine Rangger, Francesca Orlandi, Sabrina Niedermoser, Takahiro Taguchi, Björn Wängler, Clemens Decristoforo
The gastrointestinal stromal tumor (GIST) is a rare disease with limited therapeutic options when resistance to tyrosine kinase inhibitor (TKI) treatment occurs. The authors investigated binding of various (68)Ga-labeled peptides, targeting receptors reported to be overexpressed in GIST, in different cell lines. For this purpose, three GIST cell lines were tested: GIST-T1, GIST882 (Imatinib sensitive), and GIST430 (Imatinib resistant). DOTA-NT 8-13 (targeting NTR1), DOTA-TATE (targeting SSTR2), CP04 (a minigastrin derivative targeting CCK2-R), VIP-DOTA (targeting VPAC2-R), and 2 DOTA-bombesin derivatives [targeting gastrin releasing peptide receptors (GRPR)] were radiolabeled with (68)Ga and incubated with the respective tumor cell and control cell lines...
October 2016: Cancer Biotherapy & Radiopharmaceuticals
Richard Quek, Mohamad Farid, Yada Kanjanapan, Cindy Lim, Iain Beehuat Tan, Sittampalam Kesavan, Tony Kiat Hon Lim, Lynette Lin-Ean Oon, Brian Kp Goh, Weng Hoong Chan, Melissa Teo, Alexander Yf Chung, Hock Soo Ong, Wai Keong Wong, Patrick Tan, Desmond Yip
AIM: Benefit of adjuvant imatinib therapy following curative resection in patients with intermediate-risk gastrointestinal stromal tumor (GIST) is unclear. GIST-specific exon mutations, in particular exon 11 deletions, have been shown to be prognostic. We hypothesize that specific KIT mutations may improve risk stratification in patients with intermediate-risk GIST, identifying a subgroup of patients who may benefit from adjuvant therapy. METHODS: In total, 142 GIST patients with complete clinicopathologic and mutational data from two sites were included...
October 17, 2016: Asia-Pacific Journal of Clinical Oncology
Jing Huang, Leyan Wang, Chen Lu, Qun He, Yajing Xu, Fangping Chen, Xielan Zhao
OBJECTIVE: Previous studies compared the predictive ability of European Treatment Outcome Study (EUTOS), Sokal, and Hasford scoring systems and demonstrated inconsistent findings with unknown reason. This study is to determine a useful scoring system to predict the prognosis of patients with chronic myeloid leukemia (CML) and identify the probable factors that affect the scoring. MATERIALS AND METHODS: This is a retrospective cohort study. The predictive ability of EUTOS and the factors that affect scoring were analyzed in 234 Chinese CML-CP patients treated with front-line imatinib, including few patients temporarily administered hydroxyurea for cytoreduction before imatinib...
October 18, 2016: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
Adriana Borriello, Ilaria Caldarelli, Debora Bencivenga, Emanuela Stampone, Silverio Perrotta, Adriana Oliva, Fulvio Della Ragione
The hope of selectively targeting cancer cells by therapy and eradicating definitively malignancies is based on the identification of pathways or metabolisms that clearly distinguish "normal" from "transformed" phenotypes. Some tyrosine kinase activities, specifically unregulated and potently activated in malignant cells, might represent important targets of therapy. Consequently, tyrosine kinase inhibitors (TKIs) might be thought as the "vanguard" of molecularly targeted therapy for human neoplasias. Imatinib and the successive generations of inhibitors of Bcr-Abl1 kinase, represent the major successful examples of TKI use in cancer treatment...
October 13, 2016: Oncotarget
M Herbrink, N de Vries, H Rosing, A D R Huitema, B Nuijen, J H M Schellens, J H Beijnen
BACKGROUND: A liquid chromatography/tandem mass spectrometry assay was developed to facilitate therapeutic drug monitoring (TDM) for 10 anticancer compounds (dasatinib, erlotinib, gefitinib, imatinib, lapatinib, nilotinib, pazopanib, sorafenib, sunitinib, and vemurafenib) and the active metabolite, N-desethyl-sunitinib. METHODS: The TDM assay is based on reversed-phase chromatography coupled with tandem mass spectrometry in the positive ion mode using multiple-reaction monitoring for analyte quantification...
October 5, 2016: Therapeutic Drug Monitoring
Isabelle Récoché, Vanessa Rousseau, Robert Bourrel, Maryse Lapeyre-Mestre, Leila Chebane, Fabien Despas, Jean-Louis Montastruc, Emmanuelle Bondon-Guitton
Many patients treated with imatinib, used in cancer treatment, are using several other drugs that could interact with imatinib. Our aim was to study all the drug-drug interactions (DDIs) observed in patients treated with imatinib.We performed 2 observational studies, between the 1st January 2012 and the 31st August 2015 in the Midi-Pyrénées area (South Western France), using the French health insurance reimbursement database and then the French Pharmacovigilance Database (FPVD).A total of 544 patients received at least 1 reimbursement for imatinib...
October 2016: Medicine (Baltimore)
Yali Chen, Qianxiang Zhou, Lei Zhang, Ran Wang, Meihua Jin, Yuling Qiu, Dexin Kong
Increasing resistance of imatinib, a BCR-ABL tyrosine kinase inhibitor, hinders its use in the therapy of chronic myeloid leukemia (CML). The PI3K pathway is known to be closely involved in BCR-ABL transformation and the tumorigenesis of CML, suggesting that PI3K may be a potential target for CML therapy. Idelalisib, a specific inhibitor of PI3K p110δ, has been approved for the treatment of chronic lymphocytic leukemia (CLL). However, the antileukemia effect of idelalisib on CML remains unknown. In the present study, the antileukemia activity of idelalisib alone or in combination with imatinib was investigated by use of K562 cells...
October 17, 2016: Oncology Reports
Javier De Luca-Johnson, Jose I Ruades Ninfea, Lauren Pearson, Joanna Conant, Ronald Bryant, Neil A Zakai, Mary E Tang
We report the second case of ETV6-ACSL6 associated myeloproliferative neoplasm that has received a full course of imatinib therapy. The patient was a 51-year-old previously healthy man who presented with three months of worsening dyspnea and was found to have a white count of 216,000/cmm, of which 84% were eosinophil lineage. Cytogenetic analysis revealed a t(5;12)(q31~33;p13). FISH was negative for PDGFRB rearrangement but additional FISH testing demonstrated an ACSL6 rearrangement. ETV6-ACSL6 gene fusion is a rare abnormality that most often presents as a myeloproliferative-type disorder with prominent eosinophilia or basophilia...
2016: Case Reports in Medicine
Govind Babu Kanakasetty, Lakshmaiah Kuntejowdahalli, Aditi Harsh Thanky, Lokanatha Dasappa, Linu Abraham Jacob, Suresh Babu Mallekavu, Prasanna Kumari
INTRODUCTION: Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by Philadelphia (Ph) chromosome with classical t(9;22)(q34;q11) seen in up to 90% of cases. However 5% to 10% of patients who present with variant Ph translocations (vPh) have been an area of research for their significance in predicting response to various therapies including tyrosine kinase inhibitors as well as prognosticating survival outcomes for many years involving varied patient populations, with conflicting results...
September 17, 2016: Clinical Lymphoma, Myeloma & Leukemia
Lanshan Huang, Sa A Wang, Sergej Konoplev, Carlos E Bueso-Ramos, Beenu Thakral, Roberto N Miranda, Elias Jabbour, L Jeffrey Medeiros, Rashmi Kanagal-Shamanna
INTRODUCTION: Well-differentiated systemic mastocytosis (WDSM) is a rare, recently recognized provisional subvariant of systemic mastocytosis (SM). We report a case of WDSM that showed excellent clinical and cutaneous response to imatinib in the absence of known molecular genetic abnormalities. CLINICAL FINDINGS/DIAGNOSES: We present a 24-year-old woman with childhood onset of skin manifestations that progressed to mediator-related systemic events, and a gastrointestinal tract mastocytoma...
October 2016: Medicine (Baltimore)
Seyyed Mohammad Reza Hashemnia, Somayeh Atari-Hajipirloo, Shiva Roshan-Milani, Nasim Valizadeh, Sonya Mahabadi, Fatemeh Kheradmand
BACKGROUND: The anticancer agent imatinib (IM) is a small molecular analog of ATP that inhibits tyrosine kinase activity of platelet derived growth factors (PDGFs) and stem cell factor (SCF) receptor in cancer cells. However these factors have a key role in regulating growth and development of normal Sertoli, Leydig and germ cells. OBJECTIVE: The aim of this study was to determine cell viability, PDGF and SCF levels in mouse normal Sertoli cells exposed to IM. MATERIALS AND METHODS: In this experimental study, the mouse TM4 Sertoli cells were treated with 0, 2...
September 2016: International Journal of Reproductive Biomedicine (Yazd, Iran)
Susannah O'Sullivan, Mei Lin Tay, Jian-Ming Lin, Usha Bava, Karen Callon, Jillian Cornish, Dorit Naot, Andrew Grey
Nilotinib and imatinib are tyrosine kinase inhibitors (TKIs) used in the treatment of chronic myeloid leukemia (CML) and gastrointestinal stromal tumors (GIST). In vitro, imatinib and nilotinib inhibit osteoclastogenesis, and in patients they reduce levels of bone resorption. One of the mechanisms that might underlie these effects is an increase in the production of osteoprotegerin (OPG). In the current work we report that platelet-derived growth factor receptor beta (PDGFRβ) signaling regulates OPG production in vitro...
2016: PloS One
Elisabetta Fenocchio, Ilaria Depetris, Delia Campanella, Lucia Garetto, Fabrizio Carnevale Schianca, Danilo Galizia, Giovanni Grignani, Massimo Aglietta, Francesco Leone
BACKGROUND: Gemcitabine is currently the standard chemotherapy for the adjuvant treatment of pancreatic cancer. This chemotherapeutic agent is generally well-tolerated, myelosuppression and gastrointestinal toxicity being common side effects. Nevertheless, gemcitabine-induced pulmonary toxicity has been rarely reported. Despite its low incidence, the spectrum of pulmonary injury is wide, including potentially fatal conditions. We report a case of acute interstitial pneumonia related to gemcitabine, completely solved with Imatinib Mesylate (IM)...
October 12, 2016: BMC Cancer
Ya-Zhen Qin, Qian Jiang, Yue-Yun Lai, Hao Jiang, Hong-Xia Shi, Xiao-Su Zhao, Yan-Rong Liu, Xiao-Jun Huang
To investigate the impact of the combination of early molecular and cytogenetic responses on the achievement of MR4.5, 228 newly diagnosed chronic phase chronic myeloid leukemia patients treated with imatinib were categorized into 3-month and 6-month concordant optimal, discordant, concordant warning, and failure groups. Among them, 85.3% at 3 months and 78.1% at 6 months had concordant molecularly and cytogenetically defined responses. At both 3 and 6 months, patients with discordant, concordant warning and failure responses had similar 3-year MR4...
October 12, 2016: Leukemia & Lymphoma
Ayala Gover-Proaktor, Galit Granot, Saar Shapira, Oshrat Raz, Oren Pasvolsky, Arnon Nagler, Dorit L Lev, Aida Inbal, Ido Lubin, Pia Raanani, Avi Leader
Tyrosine kinase inhibitors (TKIs) have revolutionized the prognosis of chronic myeloid leukemia. With the advent of highly efficacious therapy, the focus has shifted toward managing TKI adverse effects, such as vascular adverse events (VAEs). We used an in vitro angiogenesis model to investigate the TKI-associated VAEs. Our data show that imatinib, nilotinib, and ponatinib reduce human umbilical vein endothelial cells (HUVECs) viability. Pharmacological concentrations of ponatinib induced apoptosis, reduced migration, inhibited tube formation of HUVECs, and had a negative effect on endothelial progenitor cell (EPC) function...
October 12, 2016: Leukemia & Lymphoma
Omkar Singh, Prabhat Agrawal, Ayush Agarwal, Sangeeta Yadav
No abstract text is available yet for this article.
January 2016: Journal of the Association of Physicians of India
Griger Cherry Williams, Rohan Bhise
No abstract text is available yet for this article.
January 2016: Journal of the Association of Physicians of India
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