Metabolic carbonyl reduction of anthracyclines - role in cardiotoxicity and cancer resistance. Reducing enzymes as putative targets for novel cardioprotective and chemosensitizing agents.

abstract：:Phosphatidylserine (PS) and other anionic phospholipids, which become exposed on the surface of proliferating endothelial cells, tumor cells and certain leukocytes, have been used as targets for the development of clinical-stage biopharmaceuticals. One of these products (bavituximab) is currently being investigated in...

journal_title：Investigational new drugs

authors： Bujak E,Pretto F,Neri D

更新日期：2015-08-01 00:00:00

abstract：PURPOSE:To assess the maximum well-tolerated dose (MWTD), dose limiting toxicity (DLT), pharmacokinetics (PK) and pharmacodynamics of zibotentan, a novel specific endothelin-A receptor antagonist, in patients with metastatic prostate cancer. METHODS:Patients with metastatic, castrate-resistant prostate cancer (CRPC) w...

journal_title：Investigational new drugs

authors： Schelman WR,Liu G,Wilding G,Morris T,Phung D,Dreicer R

更新日期：2011-02-01 00:00:00

abstract：:Background AR-67 is a novel camptothecin analogue at early stages of drug development. The phase 1 clinical trial in cancer patients with solid tumors was completed and a population pharmacokinetic model (POP PK) was developed to facilitate further development of this investigational agent. Methods Pharmacokinetic dat...

journal_title：Investigational new drugs

authors： Tang F,Tsakalozou E,Arnold SM,Ng CM,Leggas M

更新日期：2019-12-01 00:00:00

abstract：:Seventeen patients with small cell lung cancer entered a phase II trial testing the feasibility of adding high dose epirubicin (100-120 mg/m2, day 1) in combination with etoposide (60-80 mg/m2, days 1-5) and cisplatin (70 mg/m2, day 1) courses repeated every three weeks. Complete responders received thoracic (40 Gy) a...

journal_title：Investigational new drugs

authors： Rosell R,Carles J,Abad A,Jimeno JM,Moreno I,Barnadas A,Ribelles N,Haboubi N

更新日期：1992-07-01 00:00:00

abstract：:An HPLC analytical method was applied to the determination of plasma concentrations of 5,6-dihydro-5-azacytidine (NSC 264880, DHAC) in two foxhounds after a rapid intravenous infusion of 300 mg/kg DHAC. The dose employed is the mouse equivalent LD10 dose which results in mild reversible toxicity in the dog. The declin...

journal_title：Investigational new drugs

authors： Malspeis L,Cheng H,Staubus AE

更新日期：1983-01-01 00:00:00

abstract：PURPOSE:ZD0473 (AMD473) [cis-amminedichloro(2-methylpyridine) platinum(II)] is a novel platinum agent of proven activity in vitro against a variety of human tumor-derived cell lines even with intrinsic or acquired resistance to CDDP. The aim of this study is to provide the basis for a rational design of ZD0473-based co...

journal_title：Investigational new drugs

authors： Plasencia C,Abad A,Martinez-Balibrea E,Taron M

更新日期：2004-11-01 00:00:00

abstract：:Apoptin is a nonstructural protein encoded by one of the three open reading frames of the chicken anemia virus genome. It has attracted a great deal of interest due to its ability to induce apoptosis in multiple transformed and malignant mammalian cell lines without affecting primary and non-transformed cells. However...

journal_title：Investigational new drugs

authors： Ruiz-Martínez S,Castro J,Vilanova M,Bruix M,Laurents DV,Ribó M,Benito A

更新日期：2017-06-01 00:00:00

abstract：PURPOSE:To summarize the safety experience obtained from phase II clinical trials conducted with trabectedin as single-agent therapy in patients with advanced solid tumors. METHODS:This retrospective analysis includes 1,132 patients exposed to trabectedin in 19 phase II trials carried out between February 1999 and Apr...

journal_title：Investigational new drugs

authors： Le Cesne A,Yovine A,Blay JY,Delaloge S,Maki RG,Misset JL,Frontelo P,Nieto A,Jiao JJ,Demetri GD

更新日期：2012-06-01 00:00:00

abstract：:Background Overcoming resistance to anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) in patients with KRAS wildtype (WT) metastatic colorectal cancer (mCRC) could help meet the needs of patients with limited treatment options. Methods In this phase 1b study, patients with N/KRAS WT, MET-positi...

journal_title：Investigational new drugs

authors： Delord JP,Argilés G,Fayette J,Wirth L,Kasper S,Siena S,Mesia R,Berardi R,Cervantes A,Dekervel J,Zhao S,Sun Y,Hao HX,Tiedt R,Vicente S,Myers A,Siu LL

更新日期：2020-12-01 00:00:00

abstract：:Mezerein, the most active antitumor compound isolated from the daphne species of plants, has a structural similarity to phorbol myristate acetate (PMA), the major active compound isolated from croton oil. PMA is known to have tumor promoting activity and is a potent inflammatory agent. Mezerein has similarly been repo...

journal_title：Investigational new drugs

authors： Barton K,Randall G,Sagone AL Jr

更新日期：1989-07-01 00:00:00

abstract：:AZQ was given intravenously to 23 patients with mixed mesodermal sarcoma of the uterus refractory to conventional treatment at a dose of 22.5-30 mg/m2 q three weeks. There was one partial response lasting seven weeks and one drug-related death. Based upon the activity observed in this trial, there does not appear to b...

journal_title：Investigational new drugs

authors： Slayton RE,Blessing JA,Clarke-Pearson D

更新日期：1991-02-01 00:00:00

abstract：:Interleukin-4 (IL-4) is a pleiotropic cytokine affecting growth and differentiation of various cell types as well as regulating other cytokines. To study the effect of IL-4 on AIDS-related Kaposi's sarcoma (AIDS-KS) cells, we first examined the tumor cells for IL-4 receptor (IL-4R) expression. KS cells express a singl...

journal_title：Investigational new drugs

authors： Cai J,Zheng T,Murphy J,Waters CA,Lin GY,Gill PS

更新日期：1997-01-01 00:00:00

abstract：PURPOSE:Erlotinib (Tarceva®, OSI-774) is a small molecule inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase. As high-grade gliomas frequently show amplification, overexpression and/or mutation of EGFR, this drug has been tested in several clinical trials with glioblastoma patients, but unfortunat...

journal_title：Investigational new drugs

authors： de Vries NA,Buckle T,Zhao J,Beijnen JH,Schellens JH,van Tellingen O

更新日期：2012-04-01 00:00:00

abstract：:Background MET is a tyrosine kinase receptor involved in the regulation of cell proliferation and migration. Reported here are the phase I dose-escalation results for LY2875358, a monoclonal antibody against MET, in Japanese patients with advanced malignancies. Methods The study comprised a 3 + 3 dose-escalation part ...

journal_title：Investigational new drugs

authors： Yoh K,Doi T,Ohmatsu H,Kojima T,Takahashi H,Zenke Y,Wacheck V,Enatsu S,Nakamura T,Turner K,Uenaka K

更新日期：2016-10-01 00:00:00

abstract：:Pancreatic cancer is a lethal disease characterized by local invasion and early dissemination. It is resistant to conventional surgical, radiotherapeutic, and chemotherapeutic modalities. These interventions have had minimal impact on overall survival with very few patients enjoying long term survival. Over the past f...

journal_title：Investigational new drugs

authors： Wolff RA,Chiao P,Lenzi R,Pisters PW,Lee JE,Janjan NA,Crane CH,Evans DB,Abbruzzese JL

更新日期：2000-02-01 00:00:00

abstract：:In this study, 30 evaluable patients with advanced carcinoma of the breast were treated with cyclophosphamide 600 mg/m2 i.v. followed one day later with mitoxantrone (Novantrone; dihydroxyanthracenedione) 16 mg/m2 i.v. Drug treatment was repeated every 3-4 weeks, for a maximum of 12 cycles. The overall response rate w...

journal_title：Investigational new drugs

authors： Periti P,della Cuna GR,Pannuti F,Mazzei T,Preti P,Martoni A,Mini E

更新日期：1985-01-01 00:00:00

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：:Mitoxantrone (Novantrone; 1, 4-dihydroxy-5, 8-bis [[2-[(2-hydroxyethyl) amino]ethyl]amino-] 9, 10 anthracenedione dihydrochloride (NSC 301739] is a synthetic anthracenedione with intercalating properties. Activity has been shown in preclinical studies in mice bearing intraperitoneal P388 and L1210 leukaemias, ADJ-Pc6 ...

journal_title：Investigational new drugs

authors： Prentice HG,Wimperis JZ,Robbins G

更新日期：1985-01-01 00:00:00

abstract：:Virotherapy is an emerging strategy for the treatment of cancer that utilizes both replication-competent and genetically modified viruses to selectively kill tumor cells. We have previously shown that Coxsackievirus A21 (CVA21), a common-cold producing enterovirus, is an effective oncolytic agent against human melanom...

journal_title：Investigational new drugs

authors： Skelding KA,Barry RD,Shafren DR

更新日期：2012-04-01 00:00:00

abstract：:LY2457546 is a potent and orally bioavailable inhibitor of multiple receptor tyrosine kinases involved in angiogenic and tumorigenic signalling. In biochemical and cellular assays, LY2457546 demonstrates potent activity against targets that include VEGFR2 (KDR), PDGFRβ, FLT-3, Tie-2 and members of the Eph family of re...

journal_title：Investigational new drugs

authors： Burkholder TP,Clayton JR,Rempala ME,Henry JR,Knobeloch JM,Mendel D,McLean JA,Hao Y,Barda DA,Considine EL,Uhlik MT,Chen Y,Ma L,Bloem LJ,Akunda JK,McCann DJ,Sanchez-Felix M,Clawson DK,Lahn MM,Starling JJ

更新日期：2012-06-01 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：:The (6-maleimidocaproyl)hydrazone derivative of doxorubicin (INNO-206) is an albumin-binding prodrug of doxorubicin with acid-sensitive properties that is being assessed clinically. The prodrug binds rapidly to circulating serum albumin and releases doxorubicin selectively at the tumor site. This novel mechanism may p...

journal_title：Investigational new drugs

authors： Graeser R,Esser N,Unger H,Fichtner I,Zhu A,Unger C,Kratz F

更新日期：2010-02-01 00:00:00

abstract：:SJG-136 is a synthetic pyrrolobenzodiazepine (PBD) dimer in which two DNA-alkylating subunits are linked through an inert propanedioxy tether. Biophysical and biochemical studies of SJG-136 have shown a remarkable affinity for DNA and potent cytotoxicity in vitro. On this basis, together with its unique sequence selec...

journal_title：Investigational new drugs

authors： Wilkinson GP,Taylor JP,Shnyder S,Cooper P,Howard PW,Thurston DE,Jenkins TC,Loadman PM

更新日期：2004-08-01 00:00:00

abstract：:Twenty-four patients with a variety of solid tumors entered a Phase I trial with 4-demethoxydaunorubicin, a new analogue of daunorubicin. The drug was given as a single oral dose of 10-60 mg/m2 repeated every 3-4 weeks. Leukopenia was the dose-limiting toxicity. Other toxic effects included mild to moderate nausea and...

journal_title：Investigational new drugs

authors： Kaplan S,Sessa C,Willems Y,Pacciarini MA,Tamassia V,Cavalli F

更新日期：1984-01-01 00:00:00

abstract：:We performed an in-vitro study testing the chemosensitivity of peritoneal cancer cell lines (SW620, HCT116, MKN45, 23,132/87, OAW42) to various cytostatic drug regimens. A duplex drug, characterized by reversible linking of the antimetabolites 2'-deoxy-5-fluorouridine (5-FdU) and 3'-C-ethynylcytidine (ECyd), was compa...

journal_title：Investigational new drugs

authors： Weinreich J,Struller F,Sautkin I,Giuashvili S,Reymond M,Königsrainer A,Schott TC

更新日期：2019-06-01 00:00:00

abstract：:An inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal neoplasm that typically develops in the lungs and seldom in the head and neck region. It is often related to the anaplastic lymphoma kinase (ALK) fusion gene. Crizotinib, a first-generation ALK inhibitor, has been shown to have a notable response in pat...

journal_title：Investigational new drugs

authors： Honda K,Kadowaki S,Kato K,Hanai N,Hasegawa Y,Yatabe Y,Muro K

更新日期：2019-08-01 00:00:00

abstract：:Background This open-label, first-in-human, phase 1 study evaluated AMG 232, an oral selective MDM2 inhibitor in patients with TP53 wild-type (P53WT), advanced solid tumors or multiple myeloma (MM). Methods In the dose escalation (n = 39), patients with P53WT refractory solid tumors enrolled to receive once-daily AMG ...

journal_title：Investigational new drugs

authors： Gluck WL,Gounder MM,Frank R,Eskens F,Blay JY,Cassier PA,Soria JC,Chawla S,de Weger V,Wagner AJ,Siegel D,De Vos F,Rasmussen E,Henary HA

更新日期：2020-06-01 00:00:00

abstract：:We have developed a specific and sensitive method aiming at docetaxel (Taxotere) determination in plasma of treated patients. This involved solid-phase extraction of 1 ml of plasma onto carboxylic acid (CBA) grafted silica cartridges followed by reversed-phase liquid chromatography with UV detection. The best selectiv...

journal_title：Investigational new drugs

authors： Ardiet CJ,Tranchand B,Zanetta S,Guillot A,Bernard E,Peguy M,Rebattu P,Droz JP

更新日期：1999-01-01 00:00:00

abstract：:The poor prognosis of children with high-grade glioma (HGG) and high-risk neuroblastoma, despite multidisciplinary therapeutic approaches, demands new treatments for these indications. F14512 is a topoisomerase II inhibitor containing a spermine moiety that facilitates selective uptake by tumor cells via the Polyamine...

journal_title：Investigational new drugs

authors： Leblond P,Boulet E,Bal-Mahieu C,Pillon A,Kruczynski A,Guilbaud N,Bailly C,Sarrazin T,Lartigau E,Lansiaux A,Meignan S

更新日期：2014-10-01 00:00:00

abstract：:Background C-Met, which is frequently activated in multiple cancers, has been implicated in tumor formation, progression, metastasis, angiogenesis, and resistance to multiple therapies. MK-8033 is a small-molecule inhibitor of c-Met that binds preferentially to the activated conformation, and has demonstrated anti-tum...

journal_title：Investigational new drugs

authors： Keedy VL,Lenz HJ,Saltz L,Whisenant JG,Berlin JD,Camacho LH

更新日期：2018-10-01 00:00:00