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https://www.readbyqxmd.com/read/29137393/synergistic-effect-of-eribulin-and-cdk-inhibition-for-the-treatment-of-triple-negative-breast-cancer
#1
Shreyas S Rao, Jenna Stoehr, Danijela Dokic, Lei Wan, Joseph T Decker, Kristine Konopka, Alexandra L Thomas, Jia Wu, Virginia G Kaklamani, Lonnie D Shea, Jacqueline S Jeruss
Activation of CDK2 in triple negative breast cancer (TNBC) can contribute to non-canonical phosphorylation of a TGFβ signaling component, Smad3, promoting cell proliferation and migration. Inhibition of CDK2 was shown to decrease breast cancer oncogenesis. Eribulin chemotherapy was used effectively in the treatment of TNBC. To this end, we tested therapeutic efficacy of a novel CDK2/9 inhibitor, CYC065, eribulin, and the combination of CYC065 and eribulin in 3 different TNBC cell lines, and an in vivo xenograft model...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29110735/development-of-interstitial-pneumonia-during-treatment-with-eribulin-a-case-report
#2
Kota Nakamura, Motoyasu Kato, Yosuke Miyashita, Osamu Nagashima, Shinichi Sasaki, Shigeru Tominaga, Kazuhisa Takahashi
BACKGROUND: Eribulin is typically used to treat patients with advanced breast cancer, and anti-cancer agents often cause the development of interstitial pneumonia in Japanese patients with advanced cancer. However, few case reports have addressed eribulin-induced interstitial pneumonia. Herein, we report a rare case of interstitial pneumonia-specifically, organized pneumonia-during treatment with eribulin in a patient with advanced breast cancer. CASE PRESENTATION: A 52-year-old Japanese woman was diagnosed as having advanced breast cancer 3 years before the admission described in the present report...
November 6, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/29100327/phosphatidylinositol-3-kinase-pi3k%C3%AE-akt-axis-blockade-with-taselisib-or-ipatasertib-enhances-the-efficacy-of-anti-microtubule-drugs-in-human-breast-cancer-cells
#3
Floriana Morgillo, Carminia Maria Della Corte, Anna Diana, Concetta di Mauro, Vincenza Ciaramella, Giusi Barra, Valentina Belli, Elisena Franzese, Roberto Bianco, Evaristo Maiello, Ferdinando De Vita, Fortunato Ciardiello, Michele Orditura
Purpose: The Phosphatidylinositol 3-kinase (PI3Ks) pathway is commonly altereted in breast cancer patients, but its role is still unclear. Taselisib, a mutant PI3Kα selective inhibitor, and ipatasertib, an AKT inhibitor, are currently under investigation in clinical trials in combination with paclitaxel or hormonal therapies in breast cancer. The aim of this study was to evaluate if PI3K or AKT inhibition can prevent resistance to chemotherapy and potentiate its efficacy. Experimental design: The efficacy of combined treatment of ipatasertib and taselisib plus vinorelbine or paclitaxel or eribulin was evaluated in vitro on human breast cancer cells (with different expression profile of hormonal receptors, HER2, and of PI3Ka mutation) on cell survival by using MTT (3,(4,5-dimethylthiazol-2)2,5 difeniltetrazolium bromide) and colony forming assays on cell apoptosis by flow-cytometry analysis...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29100193/phase-ii-multicentre-randomised-trial-of-eribulin-plus-gemcitabine-versus-paclitaxel-plus-gemcitabine-as-first-line-chemotherapy-in-patients-with-her2-negative-metastatic-breast-cancer
#4
Yeon Hee Park, Seock-Ah Im, Sung-Bae Kim, Joo Hyuk Sohn, Keun Seok Lee, Yee Soo Chae, Ki Hyeong Lee, Jee Hyun Kim, Young-Hyuck Im, Ji-Yeon Kim, Tae-Yong Kim, Kyung-Hun Lee, Jin-Hee Ahn, Gun Min Kim, In Hae Park, Soo Jung Lee, Hye Sook Han, Se Hyun Kim, Kyung Hae Jung
BACKGROUND: Paclitaxel plus gemcitabine (PG) combination chemotherapy is a preferred chemotherapeutic regimen for patients with metastatic breast cancer (MBC). Eribulin mesylate is a halichondrin non-taxane inhibitor of microtubule dynamics. A recent pooled analysis with eribulin showed improved overall survival (OS) in various MBC patient subgroups pretreated with anthracycline and taxane. Furthermore, eribulin may have less neurotoxicity than paclitaxel. PATIENTS AND METHODS: This study was a prospective randomised phase II, open-label, two-arm, multicentre study comparing eribulin plus gemcitabine (EG) with PG chemotherapy as a first-line treatment for patients with human epidermal growth factor receptor 2-negative MBC...
November 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/29077412/prins-reaction-of-homoallenyl-alcohols-access-to-substituted-pyrans-in-the-halichondrin-series
#5
Hyeong-Wook Choi, Francis G Fang, Hui Fang, Dae-Shik Kim, Steven R Mathieu, Robert T Yu
Prins reaction of homoallenyl alcohols with aldehyde dimethylacetals in the presence of methoxyacetic acid directly affords tetrasubstituted pyrans relevant to halichondrins with complete control of the C27 stereogenic center. Regioselective Tsuji reduction of the resultant allylic acetates stereoselectively establishes the C25 stereogenic center and C26 exocyclic olefin. Building upon these findings, we achieved concise access to the halichondrin C14-C38 and eribulin C14-C35 fragments.
November 17, 2017: Organic Letters
https://www.readbyqxmd.com/read/29066702/-two-cases-in-which-eribulin-mesylate-was-effective-for-taxane-resistant-advanced-breast-cancer
#6
Keita Adachi, Shuhei Suzuki, Hitomi Kubota, Yukiko Hara, Asako Fujiwara, Eiko Waga, Tomohiro Hirano, Katsuhisa Enomoto, Kenichi Sakurai, Makoto Makishima, Tsugumichi Koshinaga
We experienced 2 cases in which eribulin mesylate was effective for taxane-resistant advanced breast cancer. Case 1: A 65- year-old woman was diagnosed with advanced breast cancer(T4cN2aM0, stage III B)and treated with chemotherapy(nabpaclitaxel). Bone metastasis was observed; then, she sequentially received epirubicin and cyclophosphamide, nab-paclitaxel, and bevacizumab and paclitaxel. However, lung metastases appeared, and we changed the regimen to eribulin mesylate. We administered 11 courses of eribulin mesylate before bone marrow metastasis appeared...
October 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28919822/uterine-sarcoma-current-perspectives
#7
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
#8
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
#9
Manjulika Das
No abstract text is available yet for this article.
October 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
#10
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/antitumor-effects-of-eribulin-depend-on-modulation-of-the-tumor-microenvironment-by-vascular-remodeling-in-mouse-models
#11
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. increase tumor vessels and perfusion) in human breast cancer xenograft models. However, the role of this vascular remodeling in antitumor effects is not fully understood. Here, we investigated the effects of eribulin-induced vascular remodeling on antitumor activities in multiple human cancer xenograft models. Microvessel densities (MVD) were evaluated by immunohistochemistry (CD31 staining), and antitumor effects were examined in 10 human cancer xenograft models...
November 2017: Cancer Science
https://www.readbyqxmd.com/read/28863036/clinical-activity-of-eribulin-in-advanced-desmoplastic-small-round-cell-tumor
#12
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...
October 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
#13
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
#14
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
#15
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
#16
RANDOMIZED CONTROLLED TRIAL
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...
October 20, 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-tie2-hi-macrophages-in-breast-cancer-and-pancreatic-neuroendocrine-tumors
#17
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 antiangiogenic therapy. Here, we show that the kinase switch control inhibitor rebastinib inhibits Tie2, a tyrosine kinase receptor expressed on endothelial cells and protumoral 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, antiangiogenic effects, and blockade of tumor cell intravasation mediated by perivascular Tie2(Hi)/Vegf-A(Hi) macrophages in the tumor microenvironment of metastasis (TMEM)...
November 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
#18
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
#19
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
#20
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
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