Effect of the drug transporters ABCG2, Abcg2, ABCB1 and ABCC2 on the disposition, brain accumulation and myelotoxicity of the aurora kinase B inhibitor barasertib and its more active form barasertib-hydroxy-QPA.

abstract：:Sorafenib, an orally active multi-kinase inhibitor approved for the treatment of hepatocellular carcinoma (HCC), is primarily metabolized both via cytochrome P450 3A4 isoform (CYP3A4) and UGT1A9. Due to the contribution of these two biotransformation pathways, sorafenib is considered to be less susceptible than other ...

journal_title：Investigational new drugs

authors： Gomo C,Coriat R,Faivre L,Mir O,Ropert S,Billemont B,Dauphin A,Tod M,Goldwasser F,Blanchet B

更新日期：2011-12-01 00:00:00

abstract：PURPOSE:Epidermal growth factor receptor (EGFR) inhibition may overcome chemotherapy resistance by inhibiting important anti-apoptotic signals that are constitutively activated by an overstimulated EGFR pathway. METHODS:This phase I dose escalation trial assessed the safety and efficacy of vinflunine, a novel vinca al...

journal_title：Investigational new drugs

authors： Sanoff HK,Davies JM,Walko C,Irvin W,Buie L,Keller K,Ivanova A,Chiu WK,O'Neil BH,Stinchcombe TE,Dees EC

更新日期：2011-10-01 00:00:00

abstract：PURPOSE:To assess safety and efficacy of folinic acid, 5-fluorouracil, gemcitabine (FFG) and folinic acid, fluorouracil, oxaliplatin (FOLFOX4) regimens with added bevacizumab as first-line treatment in patients with advanced colorectal cancer (CRC). PATIENTS AND METHODS:Patients with Stage III unresectable or Stage IV...

journal_title：Investigational new drugs

authors： Madajewicz S,Waterhouse DM,Ritch PS,Khan MQ,Higby DJ,Leichman CG,Malik SK,Hentschel P,Gill JF,Zhao L,Nicol SJ

更新日期：2012-04-01 00:00:00

abstract：:Radioactive iodine-refractory [(18)F] fluorodeoxy-glucose-positron emission tomography-positive thyroid carcinomas represent especially aggressive tumors. Targeting glucose metabolism by the transketolase isoenzyme transketolase like 1 (TKTL-1) which is over-expressed in various neoplasms, may be effective. The correl...

journal_title：Investigational new drugs

authors： Fröhlich E,Fink I,Wahl R

更新日期：2009-08-01 00:00:00

abstract：BACKGROUND:Lactoferrin is an iron-binding glycoprotein first identified in breast milk as a protein product of mammary epithelial cells. Its immunomodulatory functions include activation of NK and lymphokine-activated killer cells and enhancement of PMN and macrophage cytotoxicity. Studies in animal models have shown p...

journal_title：Investigational new drugs

authors： Hayes TG,Falchook GF,Varadhachary GR,Smith DP,Davis LD,Dhingra HM,Hayes BP,Varadhachary A

更新日期：2006-05-01 00:00:00

abstract：:Epidermal growth factor receptor (EGFR) gene mutations activate the KRAS-RAF-MEK-ERK pathway in lung cancer cells. EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib induce apoptosis of cancer cells, but prolonged treatment is often associated with acquired resistance. Here, we identified a novel MEK1/2 inhibito...

journal_title：Investigational new drugs

authors： Song JY,Kim CS,Lee JH,Jang SJ,Lee SW,Hwang JJ,Lim C,Lee G,Seo J,Cho SY,Choi J

更新日期：2013-12-01 00:00:00

abstract：:Polymeric cyclodextrin-based nanoparticles are currently undergoing clinical trials as nanotherapeutics. Using a non-covalent approach, we decorated two cross-linked cyclodextrin polymers of different molecular weights with an RGD peptide derivative to construct a novel carrier for the targeted delivery of doxorubicin...

journal_title：Investigational new drugs

authors： Viale M,Tosto R,Giglio V,Pappalardo G,Oliveri V,Maric I,Mariggiò MA,Vecchio G

更新日期：2019-08-01 00:00:00

abstract：:Sixteen patients with stage IV melanoma, who were heavily pretreated, received 11 mg/m2/day of intravenous Irofulven for five consecutive days every 28 days. There were no objective tumor responses, although one patient exhibited stable disease after 4 cycles. The most common toxicities were grade 1/2 nausea, vomiting...

journal_title：Investigational new drugs

authors： Pierson AS,Gibbs P,Richards J,Russ P,Eckhardt SG,Gonzalez R

更新日期：2002-08-01 00:00:00

abstract：:Fifteen patients with advanced carcinoma of the breast who had failed prior chemotherapy, were treated with recombinant gamma interferon at a dose of 2mg/m2 (1mg = 2.4 X 10(7) international units) intravenously for five consecutive days every other week. The median patient age was 51 and all patients had a performance...

journal_title：Investigational new drugs

authors： Muss HB,Caponera M,Zekan PJ,Jackson DV Jr,Stuart JJ,Richards F,Cooper MR,Levin EA,Reich SD,Capizzi RL

更新日期：1986-01-01 00:00:00

abstract：BACKGROUND:To explore the activity of lapatinib with a novel trial design focused on the drug target rather than on histology. METHODS:Patients with HER2 amplified gastro-esophageal, bladder, ovarian, or uterine tumors were enrolled into a double-blinded randomized discontinuation study of lapatinib 1,500 mg PO daily....

journal_title：Investigational new drugs

authors： Galsky MD,Von Hoff DD,Neubauer M,Anderson T,Fleming M,Nagarwala Y,Mahoney JM,Midwinter D,Vocila L,Zaks TZ

更新日期：2012-04-01 00:00:00

abstract：:Pictilisib (GDC-0941) is an oral class I phosphatidylinositol-3-phosphate kinase inhibitor. This phase Ia/Ib study investigated the safety, tolerability, pharmacokinetics, and pharmacodynamics of pictilisib in monotherapy or in combination with carboplatin-paclitaxel and bevacizumab (CP + BEV) in Japanese patients wit...

journal_title：Investigational new drugs

authors： Yamamoto N,Fujiwara Y,Tamura K,Kondo S,Iwasa S,Tanabe Y,Horiike A,Yanagitani N,Kitazono S,Inatani M,Tanaka J,Nishio M

更新日期：2017-02-01 00:00:00

abstract：:An inflammatory myofibroblastic tumor (IMT) is a rare invasive soft tissue mass with intramuscular penetration that is primarily treated via a surgical procedure. However, with unclear boundaries and a high rate of relapse, there is no standard treatment for recurrence or unresectable tumors. It is noteworthy that app...

journal_title：Investigational new drugs

authors： Liu W,Duan Q,Gong L,Yang Y,Huang Z,Guo H,Niu X

更新日期：2020-09-11 00:00:00

abstract：AIM:5,6-Dimethylxanthenone-4-acetic acid (DMXAA) (ASA404), a low molecular weight antivascular drug currently in clinical trial, acts both directly on the tumour vascular endothelium and indirectly through the induction of inflammatory cytokines and other vasoactive molecules from macrophages and other host cells. We w...

journal_title：Investigational new drugs

authors： Wang LC,Ching LM,Paxton JW,Kestell P,Sutherland R,Zhuang L,Baguley BC

更新日期：2009-06-01 00:00:00

abstract：:Survivin is expressed in tumor cells, including acute myeloid leukemia (AML), regulates mitosis, and prevents tumor cell death. The antisense oligonucleotide sodium LY2181308 (LY2181308) inhibits survivin expression and may cause cell cycle arrest and restore apoptosis in AML. In this study, the safety, pharmacokineti...

journal_title：Investigational new drugs

authors： Erba HP,Sayar H,Juckett M,Lahn M,Andre V,Callies S,Schmidt S,Kadam S,Brandt JT,Van Bockstaele D,Andreeff M

更新日期：2013-08-01 00:00:00

abstract：:Didemnin B is a depsipeptide derived from a Caribbean tunicate (sea squirt) that has demonstrated antineoplastic activity against a variety of murine tumor models, including the L1210 and P388 leukemia, the B16 melanoma, and M5076 sarcoma cell lines. Based on these data, we designed a phase II trial in which 15 patien...

journal_title：Investigational new drugs

authors： Jones DV Jr,Ajani JA,Blackburn R,Daugherty K,Levin B,Patt YZ,Abbruzzese JL

更新日期：1992-08-01 00:00:00

abstract：BACKGROUND:Although bevacizumab plus FOLFOX is a standard treatment for metastatic colorectal cancer, oxaliplatin must be withdrawn in many patients because of cumulative neurotoxicity. We postulated that a reduced dose of oxaliplatin and modified treatment schedule would prolong the time to treatment failure and evalu...

journal_title：Investigational new drugs

authors： Nakayama N,Sato A,Tanaka S,Shimada K,Konishi K,Sasaki E,Hibi K,Ichikawa H,Kikuchi Y,Sakuyama T,Sekikawa T,Hayashi K,Nishina H,Tokyo Cooperative Oncology Group, Tokyo, Japan.

更新日期：2015-08-01 00:00:00

abstract：:Purpose The aim of this study is to detect apoptotic and cytotoxic/antiproliferative effects of a ligand substance and its metal derivatives. The substances were investigated by using an h-ras oncogene transformed rat embryo fibroblast cell line (5RP7). Methods The cytotoxic influences of dipyrido[3,2-a:2',3'c]phenazi...

journal_title：Investigational new drugs

authors： Kaplan A,Benkli K,Koparal AT

更新日期：2018-10-01 00:00:00

abstract：:Menogarol is a new anthracycline undergoing phase I clinical trial. We report here the lethality after 2 hr exposure to 2 drug combinations of menogarol and several antitumor agents. A new statistical procedure was used to identify synergistic combinations. Most of these combinations were additive, except for menogaro...

journal_title：Investigational new drugs

authors： Bhuyan BK,Adams EG,Johnson M,Crampton SL

更新日期：1985-01-01 00:00:00

abstract：:Acquired resistance to tamoxifen (Tam) is a critical problem in breast cancer therapy. Therefore, new potential strategies for Tam-resistant breast cancer are needed recently. In this study, we synthesized a novel histone deacetylase (HDAC) inhibitor, MHY218, for the development of potent inhibitors of HDAC and evalua...

journal_title：Investigational new drugs

authors： Park JH,Ahn MY,Kim TH,Yoon S,Kang KW,Lee J,Moon HR,Jung JH,Chung HY,Kim HS

更新日期：2012-10-01 00:00:00

abstract：:Fluorouracil (5-FU) plus irinotecan combined with bevacizumab has significant activity in metastatic colorectal cancer (mCRC), but S-1 has become a substitute for continuous infusion of 5-FU and has a very low incidence of hand-foot syndrome. With the S-1 plus irinotecan regimen (SIR), the response rate was 62.5%, and...

journal_title：Investigational new drugs

authors： Yamada Y,Yamaguchi T,Matsumoto H,Ichikawa Y,Goto A,Kato K,Hamaguchi T,Shimada Y

更新日期：2012-08-01 00:00:00

abstract：:In an on-going Phase II evaluation, dianhydrogalactitol (NSC 132313) was administered intravenously to 28 patients with advanced or recurrent non-squamous cell carcinoma of the cervix. The initial dosage was 60 mg/m2/wk with escalation to 75 mg/m2/wk if there were no adverse effects. Twenty-seven patients were evaluab...

journal_title：Investigational new drugs

authors： Stehman FB,Blessing JA,Homesley HD,Currie JL,Yordan EL

更新日期：1984-01-01 00:00:00

abstract：INTRODUCTION:Continuous efforts from scientists of diverse fields are necessary not only to better understand the mechanism by which multidrug resistant (MDR) cancer cells occur, but also to boost the discovery of new cytotoxic compounds. This work was designed to assess the cytotoxicity and the mechanism of action of ...

journal_title：Investigational new drugs

authors： Kuete V,Sandjo LP,Djeussi DE,Zeino M,Kwamou GM,Ngadjui B,Efferth T

更新日期：2014-12-01 00:00:00

abstract：PURPOSE:Hepatobiliary cancers respond poorly to cytotoxic chemotherapy. We evaluated the activity and safety of ixabepilone, an epothilone B analogue which stabilizes microtubules, in a phase II trial in patients with advanced cancers of the gallbladder, bile duct, and liver. METHODS:Eligible patients had previously-u...

journal_title：Investigational new drugs

authors： Nimeiri HS,Singh DA,Kasza K,Taber DA,Ansari RH,Vokes EE,Kindler HL

更新日期：2010-12-01 00:00:00

abstract：:XK469 (NSC 656889) is a water-soluble member of the novel quinoxaline family of antitumor agents. In vitro, XK469 demonstrated selective cytotoxicity for several murine solid tumors including colorectal and mammary adenocarcinoma cell lines, when compared to both leukemia and normal epithelial cells. In vivo, XK469 wa...

journal_title：Investigational new drugs

authors： LoRusso PM,Parchment R,Demchik L,Knight J,Polin L,Dzubow J,Behrens C,Harrison B,Trainor G,Corbett TH

更新日期：1998-01-01 00:00:00

abstract：:Tyrosine kinase inhibitors (TKI) or monoclonal antibodies targeting EGFR, HER2 or VEGFR receptors have demonstrated substantial clinical benefit in patients with advanced breast cancer, colon cancer, head and neck cancer, non-small cell lung cancer, and renal cell carcinoma. Nevertheless, these drugs have some target ...

journal_title：Investigational new drugs

authors： Bahleda R,Massard C,Soria JC,Izzedine H,Cohen A,Ederhy S

更新日期：2010-06-01 00:00:00

abstract：:ALK-positive anaplastic large cell lymphoma (ALCL) represents a subset of non-Hodgkin's lymphoma that is treated with crizotinib, a dual ALK/MET inhibitor. Despite the remarkable initial response, ALCLs eventually develop resistance to crizotinib. ALK inhibitor resistance in tumors is a complex and heterogeneous proce...

journal_title：Investigational new drugs

authors： Li Y,Wang K,Song N,Hou K,Che X,Zhou Y,Liu Y,Zhang J

更新日期：2020-06-01 00:00:00

abstract：BACKGROUND:ONT-093 is an orally bioavailable inhibitor of P-glycoprotein (P-gp). In pre-clinical studies, ONT-093 could inhibit P-gp and reverse multidrug resistance at nM concentrations with no effect on paclitaxel pharmacokinetics. Phase I trials of ONT-093 in normal human volunteers showed no dose-limiting toxicitie...

journal_title：Investigational new drugs

authors： Chi KN,Chia SK,Dixon R,Newman MJ,Wacher VJ,Sikic B,Gelmon KA

更新日期：2005-08-01 00:00:00

abstract：:We previously found that the novel histone deacetylase inhibitor (HDACI) butyroyloxymethyl diethylphosphate (AN-7) had greater selectivity against cutaneous T-cell lymphoma (CTCL) than SAHA. AN-7 synergizes with doxorubicin (Dox), an anthracycline antibiotic that induces DNA breaks. This study aimed to elucidate the m...

journal_title：Investigational new drugs

authors： Moyal L,Goldfeiz N,Gorovitz B,Rephaeli A,Tal E,Tarasenko N,Nudelman A,Ziv Y,Hodak E

更新日期：2018-02-01 00:00:00

abstract：:Peloruside A is a microtubule-stabilizing agent that is currently under investigation as a potential anticancer agent. Peloruside A binds to a site on β-tubulin that is distinct to that of the taxanes (paclitaxel and docetaxel) and the epothilones. An attractive clinical quality of microtubule-stabilizing agents is th...

journal_title：Investigational new drugs

authors： Chan A,Singh AJ,Northcote PT,Miller JH

更新日期：2015-06-01 00:00:00

abstract：:Gemcitabine is a deoxycytidine (dCyd) analog with activity in leukemia and solid tumors, which requires phosphorylation by deoxycytidine kinase (dCK). Decreased membrane transport is a mechanism of resistance to gemcitabine. In order to facilitate gemcitabine uptake and prolong retention in the cell, a lipophilic pro-...

journal_title：Investigational new drugs

authors： Bergman AM,Adema AD,Balzarini J,Bruheim S,Fichtner I,Noordhuis P,Fodstad O,Myhren F,Sandvold ML,Hendriks HR,Peters GJ

更新日期：2011-06-01 00:00:00