Activity of the polyamine-vectorized anti-cancer drug F14512 against pediatric glioma and neuroblastoma cell lines.

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 Transport System (PTS) and increases topoisomerase II poisoning. Here, F14512 was evaluated in pediatric HGG and neuroblastoma cell lines. PTS activity and specificity were evaluated using a fluorescent spermine-coupled probe. The cytotoxicity of F14512, alone or in combination with ionizing radiation and chemotherapeutic agents, was investigated in vitro. The antitumor activity of F14512 was assessed in vivo using a liver-metastatic model of neuroblastoma. An active PTS was evidenced in all tested cell lines, providing a specific and rapid transfer of spermine-coupled compounds into cell nuclei. Competition experiments confirmed the essential role of PTS in the cell uptake and cytotoxicity of F14512. This cytotoxicity appeared greater in neuroblastoma cells compared with HGG cells but appeared independent of PTS activity levels. In vivo evaluation confirmed a marked and prolonged antitumoral effect in neuroblastoma cells. The combinations of F14512 with cisplatin and carboplatin were often found to be synergistic, and we demonstrated the significant radiosensitizing potential of F14512 in the MYCN-amplified Kelly cell line. Thus, F14512 appears more effective than etoposide in pediatric tumor cell lines, with greater efficacy in neuroblastoma cells compared with HGG cells. The synergistic effects observed with platinum compounds and the radiosensitizing effect could lead to a clinical development of the drug in pediatric oncology.

journal_name

Invest 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

doi

10.1007/s10637-014-0132-3

subject

Has Abstract

pub_date

2014-10-01 00:00:00

pages

883-92

issue

5

eissn

0167-6997

issn

1573-0646

journal_volume

32

pub_type

杂志文章
  • Pharmacokinetics of 5,6-dihydro-5-azacytidine (NSC-264880) in the foxhound.

    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

    pub_type: 杂志文章

    doi:10.1007/BF00180191

    authors: Malspeis L,Cheng H,Staubus AE

    更新日期:1983-01-01 00:00:00

  • A phase II trial of oral etoposide with mitoxantrone and ifosfamide/mesna consolidated with intravenous etoposide, methylprednisolone, high-dose arabinoside, and cisplatin as salvage therapy for relapsing and/or refractory lymphomas.

    abstract:PURPOSE:To evaluate the response to oral Etoposide when combined with mesna, ifosfamide, and mitoxantrone in patients with relapsed and/or refractory lymphoma. To evaluate response and its duration after administration of intravenous Etoposide, methylprednisolone, high-dose cytosine arabinoside, and cisplatin (ESHAP) a...

    journal_title:Investigational new drugs

    pub_type: 临床试验,杂志文章

    doi:10.1007/BF00873962

    authors: Romaguera JE,Rodriguez MA,Hagemeister FB,McLaughlin P,Swan F,Moore DF Jr,Sarris AH,Younes A,Hill D,Cabanillas F

    更新日期:1994-01-01 00:00:00

  • INNO-206, the (6-maleimidocaproyl hydrazone derivative of doxorubicin), shows superior antitumor efficacy compared to doxorubicin in different tumor xenograft models and in an orthotopic pancreas carcinoma model.

    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

    pub_type: 杂志文章

    doi:10.1007/s10637-008-9208-2

    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

  • The imidazoline compound RX871024 promotes insulinoma cell death independent of AMP-activated protein kinase inhibition.

    abstract::We have previously shown that the insulinotropic imidazoline compound RX871024 induces death of insulinoma MIN6 cells, an effect involving stimulation of c-Jun N-terminal kinase (JNK) and caspase 3. It has also been reported that AMP-activated protein kinase (AMPK) activates JNK and induces β-cell death. Here we show ...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-016-0362-7

    authors: Zaitseva II,Zaitsev SV,Berggren PO

    更新日期:2016-08-01 00:00:00

  • Crizotinib-induced simultaneous multiple cardiac toxicities.

    abstract::Crizotinib is a receptor tyrosine kinase inhibitor that has several targets, including c-ros oncogene 1 and the MET proto-oncogene. Considering its known cardiac toxicity, bradycardia is often investigated following treatment with crizotinib. Our patients had bradycardia, QT prolongation, ventricular rhythm, ventricul...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-018-0605-x

    authors: Oyakawa T,Muraoka N,Iida K,Kusuhara M,Kawamura T,Naito T,Takahashi T

    更新日期:2018-10-01 00:00:00

  • A phase 1 study of BMS-275183, a novel oral analogue of paclitaxel given on a daily schedule to patients with advanced malignancies.

    abstract:PURPOSE:BMS-275183 is an oral C-4 methyl carbonate analogue of paclitaxel that has the same mechanism of action, stabilization of tubulin polymerization. The present study was designed to: (i) assess the safety and tolerability of BMS-275183, and (ii) determine a suitable Phase II dose of BMS-275183 when given on a con...

    journal_title:Investigational new drugs

    pub_type: 杂志文章,多中心研究

    doi:10.1007/s10637-010-9498-z

    authors: Heath EI,Lorusso P,Ramalingam SS,Awada A,Egorin MJ,Besse-Hamer T,Cardoso F,Valdivieso M,Has T,Alland L,Zhou X,Belani CP

    更新日期:2011-12-01 00:00:00

  • High dose chemotherapy with autologous marrow rescue in the treatment of resistant solid tumors.

    abstract::Toxicity in the form of marrow suppression has hampered the investigation of intensive chemotherapy as it applies to the treatment of solid tumors. The use of autologous marrow rescue to ameliorate protracted aplasia permits the application of high dose chemotherapy to the treatment of solid tumors. We review the theo...

    journal_title:Investigational new drugs

    pub_type: 杂志文章,评审

    doi:10.1007/BF00177416

    authors: LeMaistre CF,Knight WA 3rd

    更新日期:1983-01-01 00:00:00

  • Phase II trial with oral idarubicin in advanced breast cancer.

    abstract::Idarubicin, a new analogue of daunorubicin, was administered to 27 patients with advanced breast cancer in a phase II trial. The drug was given orally at a dose of 30-35 mg/m2 every 3 weeks. Twenty-two patients were evaluable for response. All evaluable patients were previously treated with one or more chemotherapeuti...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/BF00172014

    authors: Lopez M,Di Lauro L,Papaldo P,Lazzaro B,Ganzina F,Di Pietro N

    更新日期:1986-01-01 00:00:00

  • Phase I clinical and pharmacokinetic study of PM01183 (a tetrahydroisoquinoline, Lurbinectedin) in combination with gemcitabine in patients with advanced solid tumors.

    abstract::Background To determine the recommended dose (RD) of a combination of PM01183 and gemcitabine in patients with advanced solid tumors. Methods Forty-five patients received escalating doses of PM01183/gemcitabine on Days 1 and 8 every 3 weeks (d1,8 q3wk) following a standard 3 + 3 design. Results PM01183 3.5 mg flat dos...

    journal_title:Investigational new drugs

    pub_type: 杂志文章,多中心研究

    doi:10.1007/s10637-016-0410-3

    authors: Paz-Ares L,Forster M,Boni V,Szyldergemajn S,Corral J,Turnbull S,Cubillo A,Teruel CF,Calderero IL,Siguero M,Bohan P,Calvo E

    更新日期:2017-04-01 00:00:00

  • Synthesis, characterization, and evaluation of Cd[L-proline]2, a novel histone deacetylase inhibitor that induces epigenetic modification of histone deacetylase isoforms in A549 cells.

    abstract::Histone deacetylases (HDACs) play an important role in the epigenetic regulation of gene expression through their effects on the compact chromatin structure. In clinical studies, several classes of histone deacetylase inhibitors (HDACi) have demonstrated potent anticancer activities with metal complexes. Hence, we syn...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-017-0489-1

    authors: Chidambaram A,Sekar A,S H K,Chidambaram RK,Arunachalam K,G P S,Vilwanathan R

    更新日期:2017-12-01 00:00:00

  • A phase II study of bevacizumab with modified OPTIMOX1 as first-line therapy for metastatic colorectal cancer: the TCOG-GI 0802 study.

    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

    pub_type: 杂志文章,多中心研究

    doi:10.1007/s10637-015-0239-1

    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

  • Current status of androgen receptor-splice variant 7 inhibitor niclosamide in castrate-resistant prostate-cancer.

    abstract::Castrate-Resistant Prostate-Cancer (CRPC) is one of the most common malignancies occurring in men. Unfortunately, even if several recently approved agents clinically improved the outcome of CRPC patients, none of these is curative especially for a splice version of the Androgen Receptor (AR) AR-V7, which is a variant ...

    journal_title:Investigational new drugs

    pub_type: 杂志文章,评审

    doi:10.1007/s10637-018-0653-2

    authors: Sobhani N,Generali D,D'Angelo A,Aieta M,Roviello G

    更新日期:2018-12-01 00:00:00

  • The notorious "drug lag" for oncology drugs in Japan.

    abstract::This study aimed to analyze the oncology "drug lag" (i.e., the delay in time required for the approval of oncology drugs) in Japan compared with that in the United States of America (US) or the European Union (EU) and to identify the factors associated with this lag. Using publicly available information, we collected ...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-011-9638-0

    authors: Yonemori K,Hirakawa A,Ando M,Hirata T,Yunokawa M,Shimizu C,Katsumata N,Tamura K,Fujiwara Y

    更新日期:2011-08-01 00:00:00

  • A phase I trial of combination trastuzumab, lapatinib, and bevacizumab in patients with advanced cancer.

    abstract:PURPOSE:Preclinical data indicate that combination HER2-directed and anti-VEGF therapy may bypass resistance to trastuzumab. A phase I trial was performed to assess safety, activity, and correlates. EXPERIMENTAL DESIGN:Patients with advanced, refractory malignancy were enrolled (modified 3 + 3 design with expansions f...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-014-0173-7

    authors: Falchook GS,Moulder S,Naing A,Wheler JJ,Hong DS,Piha-Paul SA,Tsimberidou AM,Fu S,Zinner R,Janku F,Jiang Y,Huang M,Parkhurst KL,Kurzrock R

    更新日期:2015-02-01 00:00:00

  • Distribution, elimination, metabolism and bioavailability of hexamethylenebisacetamide in rats.

    abstract::Hexamethylenebisacetamide (HMBA), an in vitro differentiating agent, was studied for its pharmacodynamic actions in animals. Plasma stability, organ distribution, excretion, oral bioavailability, and estimates of pharmacokinetic parameters and acute lethality were determined in rats. The single dose intraperitoneal LD...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/BF00179430

    authors: Litterst CL,Roth JS,Kelley JA

    更新日期:1985-01-01 00:00:00

  • Prolonged infusion gemcitabine: a clinical phase I study at low- (300 mg/m2) and high-dose (875 mg/m2) levels.

    abstract::Gemcitabine (GEM) is a novel nucleoside analogue with a unique mechanism of action. Preliminary studies have shown a mild, schedule-dependent toxic profile with a broad range of MTDs and promising antitumor activity in various solid tumors. This phase I study describes the infusion length-effect relationships of low- ...

    journal_title:Investigational new drugs

    pub_type: 临床试验,杂志文章

    doi:10.1023/a:1005817024382

    authors: Pollera CF,Ceribelli A,Crecco M,Oliva C,Calabresi F

    更新日期:1997-01-01 00:00:00

  • Cytotoxicity of withaferin A in glioblastomas involves induction of an oxidative stress-mediated heat shock response while altering Akt/mTOR and MAPK signaling pathways.

    abstract::Withaferin A (WA), a steroidal lactone derived from the plant Vassobia breviflora, has been reported to have anti-proliferative, pro-apoptotic, and anti-angiogenic properties against cancer growth. In this study, we identified several key underlying mechanisms of anticancer action of WA in glioblastoma cells. WA was f...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-012-9888-5

    authors: Grogan PT,Sleder KD,Samadi AK,Zhang H,Timmermann BN,Cohen MS

    更新日期:2013-06-01 00:00:00

  • Phase II study of didemnin B in advanced colorectal cancer.

    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

    pub_type: 临床试验,杂志文章

    doi:10.1007/BF00877248

    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

  • Down-regulation of P-cadherin with PF-03732010 inhibits cell migration and tumor growth in gastric cancer.

    abstract::P-cadherin is frequently up-regulated in solid tumors such as gastric, colon, lung, pancreatic and breast cancers. Although P-cadherin promotes cadherin-mediated cell adhesion, the gastric cancer-linked regulation of P-cadherin has not been extensively investigated. In this study, we found epigenetic regulation of P-c...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-011-9710-9

    authors: Park J,Park E,Han SW,Im SA,Kim TY,Kim WH,Oh DY,Bang YJ

    更新日期:2012-08-01 00:00:00

  • Plasma and cerebrospinal fluid pharmacokinetics of vincristine and vincristine sulfate liposomes injection (VSLI, marqibo®) after intravenous administration in Non-human primates.

    abstract:PURPOSE:Vincristine sulfate liposomes injection (VSLI, Marqibo®) is an FDA approved encapsulated preparation of standard vincristine in sphingomyelin/cholesterol liposomes. Clinical pharmacokinetics show VSLI to be a long-circulating, slow release formulation that is confined to plasma, and prior data on cerebrospinal ...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-015-0311-x

    authors: Shah NN,Cole DE,Lester-McCully CM,Wayne AS,Warren KE,Widemann BC

    更新日期:2016-02-01 00:00:00

  • Cyclosporine and alpha-difluoromethylornithine exhibit differential effects on colon and pancreatic cancer in vitro.

    abstract::alpha-Difluoromethylornithine (DFMO) is a known irreversible inhibitor of ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis. Cyclosporine (CsA) has been reported to inhibit ODC activity in vitro. In the present study, we compared the effects of DFMO and CsA on growth, survival, and poly...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/BF00175295

    authors: Saydjari R,Townsend CM Jr,Barranco SC,Thompson JC

    更新日期:1987-01-01 00:00:00

  • A phase 1 dose-escalating study of pegylated recombinant human arginase 1 (Peg-rhArg1) in patients with advanced hepatocellular carcinoma.

    abstract:BACKGROUND:Hepatocellular carcinoma (HCC) cells are auxotrophic for arginine, depletion of which leads to tumour regression. The current study evaluated safety, pharmacokinetics (PK)/ pharmacodynamics (PD) parameters, and potential anti-tumor activity of pegylated recombinant human arginase 1 (peg-rhArg1) in advanced H...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-012-9807-9

    authors: Yau T,Cheng PN,Chan P,Chan W,Chen L,Yuen J,Pang R,Fan ST,Poon RT

    更新日期:2013-02-01 00:00:00

  • Phase II trial of single-agent foretinib (GSK1363089) in patients with recurrent or metastatic squamous cell carcinoma of the head and neck.

    abstract:BACKGROUND:Foretinib is a small-molecule, oral multikinase inhibitor primarily targeting the mesenchymal epithelial transition (MET) factor receptor, and the vascular endothelial growth factor receptor 2. We conducted a phase II study to evaluate the single-agent activity and tolerability of foretinib in patients with ...

    journal_title:Investigational new drugs

    pub_type: 杂志文章,多中心研究

    doi:10.1007/s10637-012-9861-3

    authors: Seiwert T,Sarantopoulos J,Kallender H,McCallum S,Keer HN,Blumenschein G Jr

    更新日期:2013-04-01 00:00:00

  • Multicenter phase II study of amrubicin, 9-amino-anthracycline, in patients with advanced non-small-cell lung cancer (Study 1): West Japan Thoracic Oncology Group (WJTOG) trial.

    abstract:PURPOSE:Amrubicin is a novel 9-aminoanthracycline. This multicenter phase II study was conducted to evaluate the efficacy and safety of amrubicin in patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS:Sixty-one previously untreated patients with stage III or IV NSCLC were entered this study. The pat...

    journal_title:Investigational new drugs

    pub_type: 临床试验,杂志文章,多中心研究

    doi:10.1007/s10637-006-5937-2

    authors: Sawa T,Yana T,Takada M,Sugiura T,Kudoh S,Kamei T,Isobe T,Yamamoto H,Yokota S,Katakami N,Tohda Y,Kawakami A,Nakanishi Y,Ariyoshi Y

    更新日期:2006-03-01 00:00:00

  • An international, multicenter phase II trial of bortezomib in patients with hepatocellular carcinoma.

    abstract:BACKGROUND AND RATIONALE:Bortezomib (PS-341, VELCADE®) is a selective inhibitor of the 26S proteasome, an integral component of the ubiquitin-proteasome pathway. This phase II study evaluated the activity and tolerability of bortezomib in unresectable hepatocellular carcinoma (HCC) patients. METHODS:The primary endpoi...

    journal_title:Investigational new drugs

    pub_type: 杂志文章,多中心研究

    doi:10.1007/s10637-010-9532-1

    authors: Kim GP,Mahoney MR,Szydlo D,Mok TS,Marshke R,Holen K,Picus J,Boyer M,Pitot HC,Rubin J,Philip PA,Nowak A,Wright JJ,Erlichman C

    更新日期:2012-02-01 00:00:00

  • First-in-human study of the antibody DR5 agonist DS-8273a in patients with advanced solid tumors.

    abstract::Background DR5 is a transmembrane receptor that transduces extracellular ligand-binding to activate apoptosis signaling cascades. This phase 1 study evaluated the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of a new monoclonal antibody potent DR5 agonist, DS-8273a, in subjects with advanced solid...

    journal_title:Investigational new drugs

    pub_type: 杂志文章,多中心研究

    doi:10.1007/s10637-016-0420-1

    authors: Forero A,Bendell JC,Kumar P,Janisch L,Rosen M,Wang Q,Copigneaux C,Desai M,Senaldi G,Maitland ML

    更新日期:2017-06-01 00:00:00

  • Evaluation of pyrazoloacridine in patients with advanced pancreatic carcinoma.

    abstract:PURPOSE:Pyrazoloacridine (PZA) is an acridine derivative selected for clinical development because of broad pre-clinical antitumor activity and solid tumor selectivity. Phase I evaluations with PZA have demonstrated predictable toxicity and suggested clinical efficacy. A phase II trial in patients with previously untre...

    journal_title:Investigational new drugs

    pub_type: 临床试验,杂志文章

    doi:10.1023/a:1006087114621

    authors: Zalupski MM,Shields AF,Philip PA,Kraut M,LoRusso P,Heilbrun LK,Vaitkevicius V

    更新日期:1998-01-01 00:00:00

  • A phase I study of everolimus and CHOP in newly diagnosed peripheral T-cell lymphomas.

    abstract:BACKGROUND:We performed a phase I study to determine the dose and safety of everolimus as a combination chemotherapy in peripheral T-cell lymphoma (PTCL). METHODS:Four dose levels (2.5 to 10 mg) of everolimus from days 1 to 14 with CHOP (750 mg/m(2) cyclophosphamide, 50 mg/m(2) doxorubicin, and 1.4 mg/m(2) (maximum 2 ...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-013-0015-z

    authors: Kim SJ,Kang HJ,Kim JS,Eom HS,Huh J,Ko YH,Lee J,Yim DS,Lee SY,Park WS,Yang WI,Lee SS,Suh C,Kim WS

    更新日期:2013-12-01 00:00:00

  • The activity of flavone acetic acid (NSC 347512) on human colon cancer cells in vitro.

    abstract::Flavone acetic acid (FAA) was incubated for 1 to 48 hr with 3 established human colon cancer cell lines endowed with distinct degrees of phenotypic properties. All 3 lines responded to FAA in almost identical fashion; when incubated with the drug for only 1 hr, an initial decrease in survival was observed for concentr...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/BF00173501

    authors: Drewinko B,Yang LY

    更新日期:1986-01-01 00:00:00

  • Erlotinib pharmacokinetics: a critical parameter influencing acute toxicity in elderly patients over 75 years-old.

    abstract::Background Older non-small cell lung cancer (NSCLC) patients under erlotinib are reported to experience more acute toxicity. We hypothesized that modifications in erlotinib pharmacokinetics might explain this observation. Methods A monocentric prospective clinico-pharmacological study included stage IIIb/IV NSCLC cons...

    journal_title:Investigational new drugs

    pub_type: 临床试验,杂志文章

    doi:10.1007/s10637-016-0400-5

    authors: Bigot F,Boudou-Rouquette P,Arrondeau J,Thomas-Schoemann A,Tlemsani C,Chapron J,Huillard O,Cessot A,Vidal M,Alexandre J,Blanchet B,Goldwasser F

    更新日期:2017-04-01 00:00:00