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https://www.readbyqxmd.com/read/28428884/phase-i-clinical-trial-of-combination-imatinib-and-ipilimumab-in-patients-with-advanced-malignancies
#1
Matthew J Reilley, Ann Bailey, Vivek Subbiah, Filip Janku, Aung Naing, Gerald Falchook, Daniel Karp, Sarina Piha-Paul, Apostolia Tsimberidou, Siqing Fu, JoAnn Lim, Stacie Bean, Allison Bass, Sandra Montez, Luis Vence, Padmanee Sharma, James Allison, Funda Meric-Bernstam, David S Hong
BACKGROUND: Imatinib mesylate can induce rapid tumor regression, increase tumor antigen presentation, and inhibit tumor immunosuppressive mechanisms. CTLA-4 blockade and imatinib synergize in mouse models to reduce tumor volume via intratumoral accumulation of CD8+ T cells. We hypothesized that imatinib combined with ipilimumab would be tolerable and may synergize in patients with advanced cancer. METHODS: Primary objective of the dose-escalation study (3 + 3 design) was to establish the maximum tolerated dose (MTD) and recommended phase II dose...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28425854/rationale-design-synthesis-cytotoxicity-evaluation-and-molecular-docking-studies-of-1-3-4-oxadiazole-analogues
#2
Mohamed Jawed Ahsan, Arun Choupra, Rakesh Kumar Sharma, Surender Singh Jadav, Mohd Zaheen Hassan, Mohammed Afroz Bakht, Pannala Padmaja, Abdulmalik Bin Saleh Al-Tamimi, Mohammed H Geesi
We report herein, the synthesis of two new series of oxadiazole analogues, and their cytotoxicity evaluation. The oxadiazole analogues (5a-h and 12a-h) were structurally related to the heterocyclic (1,3,4- oxadiazole) linked aryl core of IMC-038525 (tubulin polymerization inhibitor), NSC 776715, and NSC 776716, with further modification by incorporating methylene linker. The title compounds (5a-h and 12a-h) were synthesized in good yields, and were characterized by IR, NMR, and mass spectral data. The cytotoxicity evaluation was carried out according to the National Cancer Institute (NCI US) Protocol against NCI-60 human cell lines derived from nine different panels...
April 19, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28424749/development-of-asymmetric-facial-depigmentation-in-a-patient-treated-with-dasatinib-with-new-onset-hypovitaminosis-d-case-report-and-review-of-the-literature
#3
Kirsten C Webb, Magdalena Harasimowicz, Monica Janeczek, Jodi Speiser, James Swan, Rebecca Tung
Dasatinib is a second-generation tyrosine kinase inhibitor (TKI) used to treat imatinib-resistant chronic myelogenous leukemia (CML), as well as other Philadelphia chromosome-positive lymphoproliferative disorders. While the most commonly reported cutaneous side effects with this therapy include a morbilliform eruption, skin exfoliation, and skin irritation, pigmentary abnormalities have also been observed, albeit much more rarely. We present the case of a 72-year-old South Asian male with CML who presented with new-onset hypopigmentation of his face and scalp three years after a dose increase of dasatinib therapy, in the setting of newly discovered borderline hypovitaminosis D...
2017: Case Reports in Dermatological Medicine
https://www.readbyqxmd.com/read/28424071/imatinib-treatment-of-poor-prognosis-mesenchymal-type-primary-colon-cancer-a-proof-of-concept-study-in-the-preoperative-window-period-impacct
#4
I Ubink, H J Bloemendal, S G Elias, M A Brink, M P Schwartz, Y C W Holierhoek, P M Verheijen, A W Boerman, R H J Mathijssen, W W J de Leng, R A de Weger, W M U van Grevenstein, M Koopman, M P Lolkema, O Kranenburg, I H M Borel Rinkes
BACKGROUND: The identification of four Consensus Molecular Subtypes (CMS1-4) of colorectal cancer forms a new paradigm for the design and evaluation of subtype-directed therapeutic strategies. The most aggressive subtype - CMS4 - has the highest chance of disease recurrence. Novel adjuvant therapies for patients with CMS4 tumours are therefore urgently needed. CMS4 tumours are characterized by expression of mesenchymal and stem-like genes. Previous pre-clinical work has shown that targeting Platelet-Derived Growth Factor Receptors (PDGFRs) and the related KIT receptor with imatinib is potentially effective against mesenchymal-type colon cancer...
April 19, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28423649/stellettin-b-induces-apoptosis-in-human-chronic-myeloid-leukemia-cells-via-targeting-pi3k-and-stat5
#5
Yali Chen, Qianxiang Zhou, Lei Zhang, Yuxu Zhong, Guanwei Fan, Zhe Zhang, Ran Wang, Meihua Jin, Yuling Qiu, Dexin Kong
Novel agents are still urgently expected for therapy of chronic myeloid leukemia (CML). The in vitro anti-leukemia activity of Stellettin B (Stel B), a triterpenoid we isolated from marine sponge Jaspis stellifera, on human CML K562 and KU812 cells was recently investigated. Stel B inhibited K562 and KU812 cell proliferation with IC50 as 0.035 μM and 0.95 μM respectively. While no obvious cell cycle arrest was observed, apoptosis was induced in K562 cells after Stel B treatment. The Stel B-induced apoptosis might be in mitochondrial pathway, with increase of Bad and Bax, decrease of Bcl-2 and activation of caspase-9...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423367/imatinib-dose-escalation-versus-sunitinib-as-a-second-line-treatment-against-advanced-gastrointestinal-stromal-tumors-a-nationwide-population-based-cohort-study
#6
Jun-Te Hsu, Puo-Hsien Le, Chang-Fu Kuo, Meng-Jiun Chiou, Chia-Jung Kuo, Tsung-Hsing Chen, Chun-Jung Lin, Jen-Shi Chen, Huang-Pin Yu, Chun-Nan Yeh, Yi-Yin Jan, Ta-Sen Yeh
BACKGROUND: Although treatment with imatinib in advanced gastrointestinal stromal tumor (GIST) patients has led to significant clinical benefits, the disease will eventually progress due to imatinib resistance. Treatment options after failure of first-line imatinib include imatinib dose escalation or shifting to sunitinib. However, there is no large-scale study to compare the efficacy difference between these two treatment strategies or the role of surgery. RESULTS: This study recruited 521 advanced GIST patients including 246, 125, and 150 placed in groups 1, 2, and 3, respectively...
April 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421416/emergence-of-ctnnb1-mutation-at-acquired-resistance-to-kit-inhibitor-in-metastatic-melanoma
#7
J Cho, S Y Kim, Y J Kim, M H Sim, S T Kim, N K D Kim, K Kim, W Park, J H Kim, K-T Jang, J Lee
PURPOSE: The KIT inhibitor, imatinib, has shown promising efficacy in patients with KIT-mutated melanoma; however, acquisition of resistance to imatinib occurs rapidly in the majority of patients. The mechanisms of acquired resistance to imatinib in melanoma remain unclear. METHODS: We analyzed biopsy samples from paired baseline and post-treatment tumor lesions in one patient with KIT-mutated melanoma who had had an initial objective tumor regression in response to imatinib treatment followed by disease progression 8 months later...
April 18, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28421351/characteristics-and-prognosis-of-rectal-gastrointestinal-stromal-tumors-an-analysis-of-registry-data
#8
Masayoshi Yasui, Toshimasa Tsujinaka, Masaki Mori, Tsuyoshi Takahashi, Yasuo Nakashima, Toshirou Nishida
PURPOSE: Rectal gastrointestinal stromal tumors (GISTs) are rare. Accordingly, their clinical features are not well-documented and optimal treatment has not been established. The objective of this study is to clarify the rates and patterns of recurrence after surgical resection of rectal GISTs, with a focus on outcomes and therapeutic modalities. METHODS: The registry was designed to collect data on rectal GISTs recorded between January, 2003 and December, 2007 at 40 participating institutions of the Kinki GIST Study Group...
April 18, 2017: Surgery Today
https://www.readbyqxmd.com/read/28420426/genotypes-of-slc22a4-and-slc22a5-regulatory-loci-are-predictive-of-the-response-of-chronic-myeloid-leukemia-patients-to-imatinib-treatment
#9
Monika Jaruskova, Nikola Curik, Rajna Hercog, Vaclava Polivkova, Eliska Motlova, Vladimir Benes, Hana Klamova, Pavla Pecherkova, Petra Belohlavkova, Filip Vrbacky, Katerina Machova Polakova
BACKGROUND: Through high-throughput next-generation sequencing of promoters of solute carrier and ATP-binding cassette genes, which encode drug transporters, we aimed to identify SNPs associated with the response to imatinib administered for first-line treatment of patients with chronic myeloid leukemia. METHODS: In silico analysis using publicly available databases was done to select the SLC and ABC genes and their promoters for the next-generation sequencing. SNPs associated with the imatinib response were identified using Fisher's exact probability tests and subjected to the linkage disequilibrium analyses with regulatory loci of concerned genes...
April 18, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28420292/neuroendocrine-tumor-of-cecum-in-patient-treated-with-imatinib-mesylate-for-blastic-phase-of-chronic-myeloid-leukemia
#10
Sabina Novaković, Anamarija Kovač Peić, Hrvoje Holik, Božena Coha
Imatinib mesylate (IM), a tyrosine kinase inhibitor, is the treatment of choice in patients with chronic myeloid leukemia (CML). It is considered a very safe drug, with mostly mild and reversible side effects. Lately, it has been suggested that adverse events may occur after a long term. We report a case of a 72-year-old woman diagnosed with blastic phase of Philadelphia chromosome positive CML treated with IM for 28 months. The patient presented first with ascites as a side effect of the drug. When the ascites re-occurred, it was caused by neuroendocrine tumor (NET) with peritoneal carcinomatosis...
April 19, 2017: Acta Clinica Belgica
https://www.readbyqxmd.com/read/28418880/contributions-of-met-activation-to-bcr-abl1-tyrosine-kinase-inhibitor-resistance-in-chronic-myeloid-leukemia-cells
#11
Masanobu Tsubaki, Tomoya Takeda, Toshiki Kino, Kazuko Sakai, Tatsuki Itoh, Motohiro Imano, Takashi Nakayama, Kazuto Nishio, Takao Satou, Shozo Nishida
Resistance to the breakpoint cluster region-abelson 1 (BCR-ABL1) tyrosine kinase inhibitor (TKI) imatinib poses a major problem when treating chronic myeloid leukemia (CML). Imatinib resistance often results from a secondary mutation in BCR-ABL1. However, in the absence of a mutation in BCR-ABL1, the basis of BCR-ABL1-independent resistance must be elucidated. To gain insight into the mechanisms of BCR-ABL1-independent imatinib resistance, we performed an array-based comparative genomic hybridization. We identified various resistance-related genes, and focused on MET...
March 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418346/extra-gastrointestinal-stromal-tumor-of-prostate
#12
Demet Etit, Haldun Kar, Neşe Ekinci, Ahmet Emre Yenipazar, Fulya Çakalağaoğlu
BACKGROUND: Extra-gastrointestinal stromal tumor is defined as a mesenchymal neoplasm arising from soft tissues outside the gastrointestinal tract. Prostatic extra-gastrointestinal stromal tumor has rarely been noted. CASE REPORT: A 56 year-old man presented with pain in the anal region. A digital rectal examination revealed that the prostate was markedly enlarged with a smooth, bulging surface. Computerized tomography images showed a 6 cm heterogeneous, infiltrative tumor within the prostate gland extending to the trigon of the bladder, left seminal vesicle and rectum...
April 5, 2017: Balkan Medical Journal
https://www.readbyqxmd.com/read/28411632/an-ultra-specific-and-sensitive-sandwich-elisa-for-imatinib-using-two-anti-imatinib-antibodies
#13
Tetsuya Saita, Yuta Yamamoto, Kazuhisa Hosoya, Yutaro Yamamoto, Sakiko Kimura, Yutaka Narisawa, Masashi Shin
The development of an immunoassay for a low-molecular-weight drug first requires the identification of specific antibodies that do not cross-react with the drug's metabolites. If two antibodies can simultaneously recognize the entire structure of the drug, we can then utilize them to establish an ultra-specific sandwich ELISA, free from interference due to the metabolic products of the drug. This paper reports an ultra-specific and sensitive sandwich ELISA for determination of the tyrosine kinase inhibitor imatinib using two anti-imatinib antibodies...
May 29, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/28410286/successful-treatment-with-imatinib-after-nilotinib-and-ipilimumab-in-a-c-kit-mutated-advanced-melanoma-patient-a-case-report
#14
Carla Murer, Pascale Kränzlin-Stieger, Lars E French, Reinhard Dummer, Simone M Goldinger
Treatment of melanoma remains a challenge in advanced disease. Recently, the molecular differentiation in BRAF-mutated, NRAS-mutated and c-kit-mutated melanomas led to new treatment strategies. Different trials show that imatinib or nilotinib lead to meaningful responses in c-kit-mutated melanoma patients. There are little published data on sequential inhibition using these two drugs in melanoma. We describe the sequential use of imatinib after nilotinib in a c-kit-mutated melanoma patient, who progressed on interferon, Allovectin, dacarbazine, nilotinib and ipilimumab, and was finally treated with the c-kit inhibitor imatinib...
April 13, 2017: Melanoma Research
https://www.readbyqxmd.com/read/28410239/homoharringtonine-suppresses-imatinib-resistance-via-the-bcl-6-p53-pathway-in-chronic-myeloid-leukemia-cell-lines
#15
Qian Wang, Wei Ding, Yihan Ding, Jingjing Ma, Zhaoye Qian, Jingxian Shao, Yufeng Li
BACKGROUND: The anti-leukemic mechanism of homoharringtonine (HHT) differs from that of IM, and HHT is one of the most useful agents for use in patients with IM resistance or intolerance. The Bcl-6/p53 pathway has been shown to regulate the sensitivity of tumor cells to antitumor drugs. We tested whether HHT blocked the Bcl-6/p53 pathway in order to promote the apoptosis of IM-resistant cells in vitro and in vivo. RESULTS: Ph+ acute lymphoblastic leukemia (ALL) cells and IM-resistant chronic myeloid leukemia (CML) cells showed high expression of Bcl-6 protein...
March 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28403779/design-synthesis-and-biological-evaluation-of-betulinic-acid-derivatives-as-new-antitumor-agents-for-leukemia
#16
Fernanda Waechter, Gloria Santos Silva, Julia Willig, Cristiane Bernardes de Oliveira, Bruna Domingues Vieira, Daniela Barreto Trivella, Aline Rigon Zimmer, Andréia Buffon, Diogo André Pilger, Simone Gnoatto
Chronic myeloid leukemia (CML) is currently treated with imatinib, a Bcr-Abl inhibitor. However, resistance to this drug usually develops over time. Triptolide, a diterpenoid triepoxide, has been shown active against CML cells resistant to imatinib, acting mainly on the level of Bcr-Abl transcription inhibition. Here, we used the triterpene betulinic acid, a known proteasome inhibitor with potential antileukemic activity, as a scaffold for the generation of analogues with predicted triptolide biological activity...
April 12, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28403552/rapid-mass-spectrometry-analysis-of-a-rectilinear-ion-trap-by-continuous-secular-frequency-scanning
#17
Xinming Huo, Jin Chen, Fei Tang, Tongtong Yao, Shiyun Piao, Kai Ni, Xiaohao Wang
RATIONALE: Secular frequency scanning is a mass spectrometry (MS) analysis method in which the frequency of the auxiliary alternating current (AC) signal is scanned. It has low requirements for radio frequency (RF) power, which is beneficial for the miniaturization of the mass spectrometer. In this study, the MS performance in the reverse secular frequency scanning (RSFS) mode is optimized for a rectilinear ion trap (RIT), and a method for rapid MS analysis using continuous secular frequency scanning (CSFS) is proposed...
April 12, 2017: Rapid Communications in Mass Spectrometry: RCM
https://www.readbyqxmd.com/read/28403213/m-copa-suppresses-endolysosomal-kit-akt-oncogenic-signalling-through-inhibiting-the-secretory-pathway-in-neoplastic-mast-cells
#18
Yasushi Hara, Yuuki Obata, Keita Horikawa, Yasutaka Tasaki, Kyohei Suzuki, Takatsugu Murata, Isamu Shiina, Ryo Abe
Gain-of-function mutations in Kit receptor tyrosine kinase result in the development of a variety of cancers, such as mast cell tumours, gastrointestinal stromal tumours (GISTs), acute myeloid leukemia, and melanomas. The drug imatinib, a selective inhibitor of Kit, is used for treatment of mutant Kit-positive cancers. However, mutations in the Kit kinase domain, which are frequently found in neoplastic mast cells, confer an imatinib resistance, and cancers expressing the mutants can proliferate in the presence of imatinib...
2017: PloS One
https://www.readbyqxmd.com/read/28401671/a-case-of-xanthoma-disseminatum-treated-with-imatinib-mesylate
#19
Gitesh U Sawatkar, Keshavamurthy Vinay, Pankaj Malhotra, Uma Nahar Saikia, Sunil Dogra
No abstract text is available yet for this article.
April 12, 2017: Dermatologic Therapy
https://www.readbyqxmd.com/read/28399894/preoperative-imatinib-mesylate-im-for-huge-gastrointestinal-stromal-tumors-gist
#20
Sumin Tang, Yuan Yin, Chaoyong Shen, Jiaju Chen, Xiaonan Yin, Bo Zhang, Yuqin Yao, Jinliang Yang, Zhixin Chen
BACKGROUND: Preoperative imatinib mesylate (IM) treatment has not yet been standardized. Here, we aim to further explore such therapy on patients with gastrointestinal stromal tumors (GIST) retrospectively. METHODS: Patients experiencing preoperative IM were identified from January 2009 to February 2015. RESULTS: A total of 28 GIST patients were identified. The patients received preoperative IM treatment for a median length of 13.5 months, ranging from 5 to 37 months...
April 11, 2017: World Journal of Surgical Oncology
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