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https://www.readbyqxmd.com/read/28919822/uterine-sarcoma-current-perspectives
#1
REVIEW
Charlotte Benson, Aisha B Miah
Uterine sarcomas comprise a group of rare tumors with differing tumor biology, natural history and response to treatment. Diagnosis is often made following surgery for presumed benign disease. Currently, preoperative imaging does not reliably distinguish between benign leiomyomas and other malignant pathology. Uterine leiomyosarcoma is the most common sarcoma, but other subtypes include endometrial stromal sarcoma (low grade and high grade), undifferentiated uterine sarcoma and adenosarcoma. Clinical trials have shown no definite survival benefit of adjuvant radiotherapy or chemotherapy and have been hampered by the rarity and heterogeneity of these disease types...
2017: International Journal of Women's Health
https://www.readbyqxmd.com/read/28911085/a-randomized-open-label-multicenter-phase-3-study-to-compare-the-efficacy-and-safety-of-eribulin-to-treatment-of-physician-s-choice-in-patients-with-advanced-non-small-cell-lung-cancer
#2
N Katakami, E Felip, D R Spigel, J-H Kim, M Olivo, M Guo, H Nokihara, J C-H Yang, N Iannotti, M Satouchi, F Barlesi
Background: Eribulin is a microtubule dynamics inhibitor with a novel mechanism of action. This phase 3 study aimed to compare overall survival (OS) in patients with heavily pretreated non-small cell lung cancer (NSCLC) receiving eribulin to treatment of physician's choice (TPC). Patients and methods: Patients with advanced NSCLC who had received ≥2 prior therapies, including platinum-based doublet and epidermal growth factor receptor tyrosine kinase inhibitor, were randomly assigned to receive eribulin or TPC (gemcitabine, pemetrexed, vinorelbine, docetaxel)...
September 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28890295/eribulin-an-effective-therapeutic-option-in-liposarcoma
#3
Manjulika Das
No abstract text is available yet for this article.
September 7, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28881742/eribulin-alone-or-in-combination-with-the-plk1-inhibitor-bi-6727-triggers-intrinsic-apoptosis-in-ewing-sarcoma-cell-lines
#4
Lilly Magdalena WeiΔ, Manuela Hugle, Simone Fulda
In this study, we investigated the molecular mechanisms of eribulin-induced cell death and its therapeutic potential in combination with the PLK1 inhibitor BI 6727 in Ewing sarcoma (ES). Here, we show that eribulin triggers cell death in a dose-dependent manner in a panel of ES cell lines. In addition, eribulin at subtoxic, low nanomolar concentrations acts in concert with BI 6727 to induce cell death and to suppress long-term clonogenic survival. Mechanistic studies reveal that eribulin monotherapy at cytotoxic concentrations and co-treatment with eribulin at subtoxic concentrations together with BI 6727 arrest cells in the M phase of the cell cycle prior to the onset of cell death...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28869796/anti-tumor-effects-of-eribulin-depend-on-the-modulation-of-tumor-microenvironment-by-vascular-remodeling-in-mouse-models
#5
Ken Ito, Shusei Hamamichi, Takanori Abe, Tsuyoshi Akagi, Hiroshi Shirota, Satoshi Kawano, Makoto Asano, Osamu Asano, Akira Yokoi, Junji Matsui, Izumi O Umeda, Hirofumi Fujii
We previously reported that eribulin mesylate (eribulin), a tubulin-binding drug (TBD), could remodel tumor vasculature (i.e., increased tumor vessels and perfusion) in human breast cancer xenograft models; however, a role of this vascular remodeling in anti-tumor effects is not fully understood. Here, we investigated the effects of eribulin-induced vascular remodeling on anti-tumor activities in multiple human cancer xenograft models. Microvessel densities (MVDs) were evaluated by immunohistochemistry (CD31 staining), and anti-tumor effects were examined in 10 human cancer xenograft models...
September 4, 2017: Cancer Science
https://www.readbyqxmd.com/read/28863036/clinical-activity-of-eribulin-in-advanced-desmoplastic-small-round-cell-tumor
#6
Sheik Emambux, Michele Kind, Francois Le Loarer, Maud Toulmonde, Eberhard Stoeckle, Antoine Italiano
Desmoplastic small round-cell tumor is a rare but highly aggressive tumor occurring mainly in adolescents and young adults. Prolonged progression-free survival has been documented in patients who have undergone aggressive multimodality therapy - that is, multiagent intensive chemotherapy, debulking surgery, and radiation therapy. Eribulin is a microtubule-dynamics inhibitor, and it has recently been shown to be active in liposarcomas. In preclinical models, eribulin activities have also been shown to occur in Ewing's sarcoma cell lines, rhabdomyosarcomas and osteosarcomas...
August 31, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28862627/analysis-of-the-microvascular-morphology-and-hemodynamics-of-breast-cancer-in-mice-using-spring-8-synchrotron-radiation-microangiography
#7
Masae Torii, Toshifumi Fukui, Masashi Inoue, Shotaro Kanao, Keiji Umetani, Mikiyasu Shirai, Tadakatsu Inagaki, Hirotsugu Tsuchimochi, James T Pearson, Masakazu Toi
Tumor vasculature is characterized by morphological and functional abnormalities. However, analysis of the dynamics in blood flow is still challenging because of limited spatial and temporal resolution. Synchrotron radiation (SR) microangiography above the K-edge of the iodine contrast agent can provide high-contrast imaging of microvessels in time orders of milliseconds. In this study, mice bearing the human breast cancer cell lines MDAMB231 and NOTCH4 overexpression in MDAMB231 (MDAMB231(NOTCH4+)) and normal mice were assessed using SR microangiography...
September 1, 2017: Journal of Synchrotron Radiation
https://www.readbyqxmd.com/read/28861862/phase-i-dose-finding-study-of-eribulin-and-capecitabine-for-metastatic-breast-cancer-jbcrg-18-cape-study
#8
Masaya Hattori, Hiroshi Ishiguro, Norikazu Masuda, Akiyo Yoshimura, Shoichiro Ohtani, Hiroyuki Yasojima, Satoshi Morita, Shinji Ohno, Hiroji Iwata
BACKGROUND: Eribulin is a nontaxane microtubule inhibitor with activity in patients with metastatic breast cancer (MBC). We conducted a phase I dose-finding study of eribulin and capecitabine in patients with MBC pretreated with anthracycline and taxane. METHODS: Women with MBC aged ≤70 years were enrolled. A 3 + 3 dose escalation design was used: level 0 dosing, eribulin (1.4 mg/m(2) intravenously on days 1 and 8) plus capecitabine [825 mg/m(2) orally twice daily (BID)]; 2-weeks-on, 1-week-off in a 21-day cycle...
August 31, 2017: Breast Cancer: the Journal of the Japanese Breast Cancer Society
https://www.readbyqxmd.com/read/28859615/identification-of-predictive-markers-of-the-therapeutic-effect-of-eribulin-chemotherapy-for-locally-advanced-or-metastatic-breast-cancer
#9
Shinichiro Kashiwagi, Wakaba Fukushima, Yuka Asano, Wataru Goto, Koji Takada, Satoru Noda, Tsutomu Takashima, Naoyoshi Onoda, Masahiko Ohsawa, Kosei Hirakawa, Masaichi Ohira
BACKGROUND: The recently developed reagent, eribulin mesylate (eribulin), is a microtubule dynamics inhibitor with a mechanism of action that differs from those of taxanes and vinca alkaloids. This drug is considered to be a promising chemotherapeutic agent for the treatment of locally advanced or metastatic breast cancer (MBC). In this study, we investigated if variables such as tumor expression of β-tubulin class III, glutathione S-transferase pi (GSTP) 1 or transducin-like enhancer of split (TLE) 3 might act as predictive factors on the therapeutic effect of eribulin chemotherapy...
August 31, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28854066/activity-of-eribulin-in-patients-with-advanced-liposarcoma-demonstrated-in-a-subgroup-analysis-from-a-randomized-phase-iii-study-of-eribulin-versus-dacarbazine
#10
George D Demetri, Patrick Schöffski, Giovanni Grignani, Jean-Yves Blay, Robert G Maki, Brian A Van Tine, Thierry Alcindor, Robin L Jones, David R D'Adamo, Matthew Guo, Sant Chawla
Purpose A phase III study comparing eribulin with dacarbazine in patients with advanced liposarcoma (LPS) or leiomyosarcoma showed a significant improvement in overall survival (OS) for the eribulin arm, with a manageable toxicity profile. We now report the histology-specific subgroup analysis of the efficacy and safety of eribulin compared with dacarbazine in patients with LPS, an independently randomized stratified subgroup of this phase III trial. Methods Patients ≥ 18 years with advanced or metastatic dedifferentiated, myxoid/round cell, or pleomorphic LPS incurable by surgery or radiotherapy were included...
August 30, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28838996/the-selective-tie2-inhibitor-rebastinib-blocks-recruitment-and-function-of-tie2hi-macrophages-in-breast-cancer-and-pancreatic-neuroendocrine-tumors
#11
Allison S Harney, George S Karagiannis, Jeanine Pignatelli, Bryan D Smith, Ece Kadioglu, Scott C Wise, Molly M Hood, Michael D Kaufman, Cynthia B Leary, Wei-Ping Lu, Gada Al-Ani, Xiaoming Chen, David Entenberg, Maja H Oktay, Yarong Wang, Lawrence Chun, Michele De Palma, Joan G Jones, Daniel L Flynn, John S Condeelis
Tumor-infiltrating myeloid cells promote tumor progression by mediating angiogenesis, tumor cell intravasation and metastasis, which can offset the effects of chemotherapy, radiation, and anti-angiogenic therapy. Here, we show that the kinase switch control inhibitor rebastinib inhibits Tie2, a tyrosine kinase receptor expressed on endothelial cells and pro-tumoral Tie2-expressing macrophages in mouse models of metastatic cancer. Rebastinib reduces tumor growth and metastasis in an orthotopic mouse model of metastatic mammary carcinoma through reduction of Tie2+ myeloid cell infiltration, anti-angiogenic effects, and blockade of tumor cell intravasation mediated by perivascular Tie2Hi/Vegf-AHi macrophages in the tumor microenvironment of metastasis (TMEM)...
August 24, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28810913/selinexor-kpt-330-demonstrates-anti-tumor-efficacy-in-preclinical-models-of-triple-negative-breast-cancer
#12
Natalia Paez Arango, Erkan Yuca, Ming Zhao, Kurt W Evans, Stephen Scott, Charissa Kim, Ana Maria Gonzalez-Angulo, Filip Janku, Naoto T Ueno, Debu Tripathy, Argun Akcakanat, Aung Naing, Funda Meric-Bernstam
BACKGROUND: Selinexor (KPT-330) is an oral agent that has been shown to inhibit the nuclear exporter XPO1. Given the pressing need for novel therapies for triple-negative breast cancer (TNBC), we sought to determine the antitumor effects of selinexor in vitro and in vivo. METHODS: Twenty-six breast cancer cell lines of different breast cancer subtypes were treated with selinexor in vitro. Cell proliferation assays were used to measure the half-maximal inhibitory concentration (IC50) and to test the effects in combination with chemotherapy...
August 15, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28761747/eribulin-for-metastatic-breast-cancer-mbc-treatment-a-retrospective-multicenter-study-based-in-campania-south-italy-eri-001-trial
#13
Michele Orditura, Adriano Gravina, Ferdinando Riccardi, Anna Diana, Carmela Mocerino, Luigi Leopaldi, Alessio Fabozzi, Guido Giordano, Raffaele Nettuno, Pasquale Incoronato, Maria Luisa Barzelloni, Roberta Caputo, Agata Pisano, Giuseppe Grimaldi, Geppino Genua, Vincenzo Montesarchio, Enrico Barbato, Giovanni Iodice, Eva Lieto, Eugenio Procaccini, Roberto Mabilia, Antonio Febbraro, Michelino De Laurentiis, Fortunato Ciardiello
BACKGROUND: On the basis of the results of two pivotal phase III clinical trials, eribulin mesylate is currently approved in EU for the treatment of advanced breast cancer (aBC) in patients who have previously received an anthracycline and a taxane in either the adjuvant or the metastatic setting, and at least one chemotherapeutic regimen for metastatic disease. METHODS: In our study, we investigated the efficacy and tolerability of eribulin as second or further line chemotherapy in 137 women affected by aBC...
2017: ESMO Open
https://www.readbyqxmd.com/read/28741868/retrospective-analysis-of-the-efficacy-and-safety-of-eribulin-therapy-for-metastatic-breast-cancer-in-daily-practice
#14
Toshihiro Tanaka, Miho Ueno, Yuta Nakashima, Shotaro Chinen, Eiichi Sato, Michio Masaki, Ai Mogi, Hidenori Sasaki, Kazuo Tamura, Yasushi Takamatsu
BACKGROUND: Evidence of eribulin therapy for metastatic breast cancer (MBC) in clinical practice is not well documented. METHODS: We retrospectively analyzed the safety and efficacy of eribulin in 29 MBC patients from 2011 to 2016 at Fukuoka University Hospital. RESULTS: The median patient age, number of courses, total dose, and relative dose intensity were as follows: 65 years, five courses, 8.6 mg/m(2) , and 75%, respectively. One patient achieved a complete response, (CR) six a partial response (PR), eight stable disease (SD) and 14 patients exhibited progressive disease...
September 2017: Thoracic Cancer
https://www.readbyqxmd.com/read/28739698/highly-eribulin-resistant-kbv20c-oral-cancer-cells-can-be-sensitized-by-co-treatment-with-the-third-generation-p-glycoprotein-inhibitor-elacridar-at-a-low-dose
#15
Yujin Park, Ji-Yeon Son, Byung-Mu Lee, Hyung Sik Kim, Sungpil Yoon
BACKGROUND/AIM: Eribulin mesylate, also called Halaven® (HAL), was recently developed as a microtubule-targeting drug and is used in the clinic for resistant or metastatic cancer. Previously, we showed that P-glycoprotein (P-gp)-overexpressing KBV20C oral cancer cells are highly resistant to HAL compared to sensitive KB cells. This qualitative study was designed to identify specific P-gp inhibitors that increase the sensitivity of highly resistant cancer cells to HAL. MATERIALS AND METHODS: In order to identify functional P-gp inhibitors, HAL-treated KBV20C cells were co-treated with P-gp inhibitors, verapamil, elacridar, cyclosporine A, mitotane, piperine, fumagillin, curcumin, indomethacin, probenecid, sulindac, tesmilifene, and C-4...
August 2017: Anticancer Research
https://www.readbyqxmd.com/read/28698435/-histology-specific-chemotherapy-in-soft-tissue-sarcomas
#16
Eisuke Kobayashi, Akira Kawai
Soft-tissue sarcomas(STSs)are rare mesenchymal tumors, accounting for less than 1%of all adult malignancies. STSs also have diversity, with more than 50 different histological subtypes. While surgical complete resection is a definitive treatment for localized STS, chemotherapy is the treatment option for managing locally advanced and metastatic STS. Although doxorubicin ±ifosfamide is still the first-line therapy for most STS subtypes, some STSs(alveolar soft part sarcoma, clear cell sarcoma, epithelioid sarcoma and extraskeletal myxoid chondrosarcoma)have been reported to have little response to these cytotoxic chemotherapies...
June 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28698434/-the-role-of-novel-agents-in-the-treatment-of-soft-tissue-sarcoma
#17
Yoichi Naito
Soft tissue sarcomas are rare disease and the development of efficacious drug is urgently needed. The challenge is continuing, and recently 2 drugs, trabectedin and eribulin, were approved in Japan. Both drugs were investigated in patients with liposarcoma or leiomyosarcoma in randomized phase III trials as compared to dacarbazine. Eribulin was superior in terms of overall survival and trabectedin was superior in terms of progression-free survival compared to dacarbazine. This article reviews the efficacy and safety of both drugs...
June 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28681998/eribulin-regresses-a-doxorubicin-resistant-ewing-s-sarcoma-with-a-fus-erg-fusion-and-cdkn2a-deletion-in-a-patient-derived-orthotopic-xenograft-pdox-nude-mouse-model
#18
Kentaro Miyake, Takashi Murakami, Tasuku Kiyuna, Kentaro Igarashi, Kei Kawaguchi, Yunfeng Li, Arun S Singh, Sarah M Dry, Mark A Eckardt, Yukihiko Hiroshima, Masashi Momiyama, Ryusei Matsuyama, Takashi Chishima, Itaru Endo, Fritz C Eilber, Robert M Hoffman
Ewing's sarcoma is a recalcitrant tumor greatly in need of more effective therapy. The aim of this study was to determine the efficacy of eribulin on a doxorubicin (DOX)-resistant Ewing's sarcoma patient derived orthotopic xenograft (PDOX) model. The Ewing's sarcoma PDOX model was previously established in the right chest wall of nude mice from tumor resected form the patient's right chest wall. In the previous study, the Ewing's sarcoma PDOX was resistant to doxorubicin (DOX) and sensitive to palbociclib and linsitinib...
July 6, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28679691/metastatic-triple-negative-breast-cancer-patient-with-tp53-tumor-mutation-experienced-11-months-progression-free-survival-on-bortezomib-monotherapy-without-adverse-events-after-ending-standard-treatments-with-grade-3-adverse-events
#19
Tobias Meißner, Adam Mark, Casey Williams, Wolfgang E Berdel, Stephanie Wiebe, Andrea Kerkhoff, Eva Wardelmann, Timo Gaiser, Carsten Müller-Tidow, Philip Rosenstiel, Norbert Arnold, Brian Leyland-Jones, Andre Franke, Martin Stanulla, Michael Forster
A triple-negative breast cancer patient had no hereditary BRCA1, BRCA2, or TP53 risk variants. After exhaustion of standard treatments, she underwent experimental treatments and whole-exome sequencing of tumor, blood, and a metastasis. Well-tolerated experimental bortezomib monotherapy was administered for a progression-free period of 11 mo. After progression, treatments were changed and the exome data were evaluated, expanded with RNA and exome sequencing of a late-stage metastasis. In the final stage, eribulin alone and in combination with anthracyclines were administered...
July 2017: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/28664226/eribulin-shows-high-concentration-and-long-retention-in-xenograft-tumor-tissues
#20
Michiko Sugawara, Krista Condon, Earvin Liang, Christopher DesJardins, Edgar Schuck, Kazutomi Kusano, W George Lai
PURPOSE: Eribulin, a synthetic analog of the natural product halichondrin B, is a microtubule dynamics inhibitor. In this study, we report the pharmacokinetic profiles of eribulin in mice, rats, and dogs following intravenous administrations with optimized and validated bio-analytical methods. METHODS: Eribulin was administered at 0.5 and 2 mg/kg in mice, 0.5 and 1 mg/kg in rats, and 0.08 mg/kg in dogs. Tumor and brain penetration of eribulin was also evaluated in LOX human melanoma xenograft models...
August 2017: Cancer Chemotherapy and Pharmacology
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