Abstract:
:Cribrostatin 6 is a quinone-containing natural product that induces the death of cancer cell lines in culture, and its mechanism of action and scope of activity are unknown. Here we show that cribrostatin 6 has broad anticancer activity, potently inducing apoptotic cell death that is not preceded by any defined cell cycle arrest. Consistent with this data, we find that cribrostatin 6 treated cells have large amounts of reactive oxygen species (ROS) and, based on transcript profiling experiments and other data, this ROS generation is likely the primary mechanism by which cribrostatin 6 induces apoptosis. Given the success of certain ROS producers as anticancer agents, cribrostatin 6 has potential as a novel chemotherapeutic agent.
journal_name
Invest New Drugsjournal_title
Investigational new drugsauthors
Hoyt MT,Palchaudhuri R,Hergenrother PJdoi
10.1007/s10637-010-9390-xsubject
Has Abstractpub_date
2011-08-01 00:00:00pages
562-73issue
4eissn
0167-6997issn
1573-0646journal_volume
29pub_type
杂志文章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
pub_type: 杂志文章
doi:10.1007/s10637-005-3690-6
更新日期:2006-05-01 00:00:00
abstract::In a previous study we reported on the synthesis of 1,4-naphthoquinone-sulfides by thiolation of 1,4-naphthohydroquinones with primary aryl and alkyl thiols using laccase as catalyst. These compounds were synthesized as Vitamin K3 analogues. Vitamin K3 (VK3; 2-methyl-1,4-naphthoquinone; menadione) is known to have pot...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-019-00855-8
更新日期:2020-04-01 00:00:00
abstract::This dose-escalating phase I clinical trial was designed to determine the recommended dose (RD) and to assess the safety and feasibility of weekly plitidepsin (1-hour i.v. infusion, Days 1, 8 and 15) combined with carboplatin (1-hour i.v. infusion, Day 1, after plitidepsin) in 4-week (q4wk) cycles given to patients wi...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-010-9488-1
更新日期:2011-12-01 00:00:00
abstract::The study investigated possible mechanisms by which second-generation taxanes, established as significantly more effective than paclitaxel in vitro, suppress a rat lymphoma model in vivo. The studied mechanisms included taxane pharmacokinetics, expression of genes dominating their metabolism (Cyp3a1/2) and transport (...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-011-9654-0
更新日期:2012-06-01 00:00:00
abstract::We explored whether barasertib (AZD1152), a selective Aurora B kinase inhibitor, is a substrate for P-glycoprotein (Pgp, MDR1), breast cancer resistance protein (BCRP), and multidrug resistance protein 2 (MRP2) in vitro. Cell survival, drug transport, and competition experiments with barasertib pro-drug and the more a...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-013-9923-1
更新日期:2013-10-01 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
pub_type: 杂志文章
doi:10.1007/s10637-008-9167-7
更新日期:2009-06-01 00:00:00
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
更新日期:2016-08-01 00:00:00
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
更新日期:2006-03-01 00:00:00
abstract:BACKGROUND:We evaluated the efficacy and safety of cetuximab in combination with XELOX [XELoda® (capecitabine) and OXaliplatin] in advanced gastric cancer (AGC) patients. The objectives were to evaluate overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety of cetuximab plus XEL...
journal_title:Investigational new drugs
pub_type: 杂志文章,多中心研究
doi:10.1007/s10637-009-9363-0
更新日期:2011-04-01 00:00:00
abstract::Artemisinin and its derivatives are well known antimalarial drugs, particularly useful after resistance to traditional antimalarial pharmaceuticals has started to occur in Plasmodium falciparum. In recent years, anticancer activity of artemisinin has been reported both in vitro and in vivo. Artemisinin has inhibitory ...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-008-9188-2
更新日期:2009-10-01 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
pub_type: 杂志文章
doi:10.1007/s10637-011-9752-z
更新日期:2012-10-01 00:00:00
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
更新日期:1998-01-01 00:00:00
abstract::B cell prolymphocytic leukemia (B-PLL) is a rare and aggressive disease that is associated with poor survival. Although initially asymptomatic patients do not require therapy, most patients will progress and inevitably require treatment. More than 50% of patients with B-PLL carry abnormalities in the TP53 tumor suppre...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-020-00902-9
更新日期:2020-10-01 00:00:00
abstract::Neuroblastoma is an extracranial, solid, and heterogeneous malignancy in children. The conventional therapeutic modalities are mostly ineffective and thus new therapeutic strategies for malignant neuroblastoma are urgently warranted. We examined the synergistic efficacy of combination of sorafenib (SF) and genistein (...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-009-9324-7
更新日期:2010-12-01 00:00:00
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
更新日期:2011-12-01 00:00:00
abstract::Thirty-two patients with advanced epidermoid carcinoma of the esophagus were treated with ifosfamide (1.50 gm/m2 daily x 5 days) with uroprotective mesna in a phase II study. Eighteen patients were previously untreated. Of 28 evaluable patients, two (7%) had partial remissions lasting 2+ and 6+ months. Toxicity was pr...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/BF00175406
更新日期:1988-09-01 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
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1007/BF00194555
更新日期:1991-02-01 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
pub_type: 杂志文章
doi:10.1007/BF00175387
更新日期:1984-01-01 00:00:00
abstract::Fifteen patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck received a 5 day continuous I.V. infusion of 6-thioguanine repeated every five weeks. Dose limiting toxicity was primarily hematological with grade III/IV leucopenia and thrombocytopenia seen in seven patients. Nausea and vo...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
doi:10.1007/BF00873122
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
pub_type: 杂志文章
doi:10.1007/BF00180191
更新日期:1983-01-01 00:00:00
abstract::Background Metformin use is associated with reduced cancer risk in epidemiological studies and has preclinical anti-cancer activity in ovarian cancer models. The primary objective of this phase I study was to determine the recommended phase II dose (RP2D) of metformin in combination with carboplatin/paclitaxel in pati...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-020-00920-7
更新日期:2020-10-01 00:00:00
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
更新日期:1986-01-01 00:00:00
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
更新日期:1997-01-01 00:00:00
abstract::Androgen receptors are present in both pancreatic cancer tissue and cell lines. Flutamide is a potent antiandrogen widely used in clinical practice for patients with metastatic prostate cancer. This Phase II trial was undertaken to evaluate the impact of flutamide in patients with advanced pancreatic adenocarcinoma wh...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
doi:10.1023/a:1005989519350
更新日期:1997-01-01 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
pub_type: 杂志文章,多中心研究
doi:10.1007/s10637-015-0239-1
更新日期:2015-08-01 00:00:00
abstract:BACKGROUND:To evaluate the safety and tolerability of two different weekly doses of the fully humanized epidermal growth factor receptor (EGFR)-targeting monoclonal antibody matuzumab combined with high-dose 5-fluorouracil, leucovorin and cisplatin (PLF) in the first-line treatment of patients with EGFR-positive advanc...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-012-9848-0
更新日期:2013-06-01 00:00:00
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
更新日期:2012-02-01 00:00:00
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
更新日期:2013-06-01 00:00:00
abstract::An automated in vitro technique for drug toxicity testing is described. Human tumor cells were cultured for 2 days in 96-well microtiter plates before the addition of serial dilutions of drugs. At day 5 the cultures were terminated by the addition of a solution containing propidium iodide, ink and triton X-100 (PIT). ...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/BF00203541
更新日期:1987-01-01 00:00:00
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
更新日期:1983-01-01 00:00:00