Abstract:
:Cis-diaminechloro-[2-(diethylamino) ethyl 4-amino-benzoate, N(4)]-chloride platinum (II) monohydrochloride monohydrate (DPR) is a new platinum triamine complex obtained from the synthesis of cisplatin and procaine. In this paper we analyzed, adopting a disease-oriented strategy, the tumour selectivity of this compound, its ability to induce apoptosis and its mechanism of interaction with DNA. The inhibition of cell proliferation was evaluated by the MTT assay using a panel of 51 tumour cell lines. Some of them were also evaluated for the induction of apoptosis by 4'-6-diamidine-2'-phenylindole (DAPI) staining, Western blot of p53 protein and agarose gel electrophoresis of ladder DNA. Finally, interstand cross-links (ISCL) were evaluated by ethidium bromide fluorescence technique. When evaluated by the MTT assay, DPR showed a high selective activity for neuroblastoma, small cell lung cancer (SCLC), ovarian cancer and leukemia cell lines. The comparison of mean graphs of DPR and cisplatin suggested that our compound possesses a mechanism of action similar to that, at least in part, of its parent compound. Moreover, DPR showed itself to be a good trigger of programmed cell death, as demonstrated by DAPI staining, activation of p53 protein and agarose gel electrophoresis of ladder DNA. Finally, the study of the formation of ISCLs demonstrated that DPR, despite being a monofunctional platinum compound, is able to form bifunctional adducts through the release of procaine residue. Data presented here suggest that DPR is an antitumour agent able to trigger apoptosis, and that it is endowed with a peculiar mechanism(s) of action and a special selective activity against two tumours, namely neuroblastoma and SCLC, which are still characterized by a low incidence of long-term survivors.
journal_name
Invest New Drugsjournal_title
Investigational new drugsauthors
Mariggiò MA,Cafaggi S,Ottone M,Parodi B,Vannozzi MO,Mandys V,Viale Mdoi
10.1023/b:drug.0000006170.38419.c9subject
Has Abstractpub_date
2004-01-01 00:00:00pages
3-16issue
1eissn
0167-6997issn
1573-0646pii
5151109journal_volume
22pub_type
杂志文章abstract::Fifteen patients with advanced, cisplatin-refractory germ cell tumors (GCT) were treated with iproplatin (CHIP). No objective responses were noted in any of the patients treated. By restricting the entry criteria to heavily pre-treated patients, the identification of new active agents in phase II trials may be hindere...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
doi:10.1007/BF00944190
更新日期:1992-11-01 00:00:00
abstract::Spirogermanium (NSC 192965) is a new metallic investigational anticancer drug of novel heterocyclic structure. Although its mode of action has not been fully elucidated, it appears that spirogermanium is not a phase or cell cycle specific drug and inhibits DNA, RNA and protein synthesis, the protein synthesis being th...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/BF00208894
更新日期:1983-01-01 00:00:00
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
更新日期:2018-10-01 00:00:00
abstract::Twenty-six patients with advanced, measurable epithelial carcinoma of the ovary were treated with 76 courses of esorubicin at doses ranging from 20-30 mg/m2 every 3 weeks. All patients are evaluable for toxicity and response. All patients had received prior therapy including radiation therapy in 9, non-anthracycline c...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/BF00173763
更新日期:1989-11-01 00:00:00
abstract::An in vitro assay, which evaluates drug effect on 3H-thymidine incorporation, was used to investigate the absolute and relative activities of cisplatin (DDP), carboplatin (CBDCA) and iproplatin (CHIP) on 317 specimens from untreated tumors, including breast and ovarian cancers and malignant melanomas. Similar activiti...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/BF00175294
更新日期:1987-01-01 00:00:00
abstract::Drug lag, which delays patients' access to medicinal products, is typically associated with pharmaceutical regulations. To shorten drug lag, health authorities may establish new policies to liberalize the regulations, a step that is important in countries, such as Taiwan, with consumer demand for imported novel therap...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-018-00715-x
更新日期:2019-10-01 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
pub_type: 杂志文章
doi:10.1007/s10637-009-9252-6
更新日期:2010-06-01 00:00:00
abstract::Objective The aim of the current study was to examine the anticancer activity and the detailed mechanism of novel diisoquinoline derivatives in human gastric cancer cells (AGS). Methods The viability of AGS cells was measured by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Cell cycle analy...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-018-0584-y
更新日期:2018-12-01 00:00:00
abstract::Ninhydrin (2,2-dihydroxy-1,3-indane dione) was evaluated for its antitumor and cytotoxic properties in Ehrlich ascites carcinoma cell (EAC Cell)-bearing mice. The rationale behind this study has been mainly the literature reports of its characteristic interference with DNA synthesis and calcium homeostasis. Antitumor ...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1023/a:1006465504723
更新日期:2000-08-01 00:00:00
abstract::The combination of anti-cancer drugs with nutritional factors is a potential strategy for improving the efficacy of chemotherapy, particularly for hepatocellular carcinoma because its conventional therapies are mostly ineffective. Using a highly invasive hepatoma SK-Hep-1 cell line, we investigated the possible synerg...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-011-9727-0
更新日期:2012-08-01 00:00:00
abstract::Preclinical studies, along with Phase I, II, and III clinical trials demonstrate the pharmacokinetics, pharmacodynamics, safety and efficacy of a new drug under well controlled circumstances in relatively homogeneous populations. However, these types of studies generally do not answer important questions about variabi...
journal_title:Investigational new drugs
pub_type: 杂志文章,评审
doi:10.1023/a:1023525513696
更新日期:2003-05-01 00:00:00
abstract:BACKGROUND:Docetaxel-prednisone (DP) is an approved therapy for metastatic castration-resistant prostate cancer (mCRPC). Orteronel (TAK-700) is an investigational, selective, non-steroidal inhibitor of 17,20-lyase, a key enzyme in androgenic hormone production. This phase 1/2 study evaluated orteronel plus DP in mCRPC ...
journal_title:Investigational new drugs
pub_type: 杂志文章,多中心研究
doi:10.1007/s10637-014-0199-x
更新日期:2015-04-01 00:00:00
abstract:BACKGROUND:Based on reports of the efficacy of docetaxel (T) in STS, we undertook a phase I/II trial to determine the response rate (RR), dose-limiting toxicity (DLT), and maximum tolerated dose (MTD) of addition of T to doxorubicin (A) and ifosfamide (I) in advanced STS. METHODS:Patients with advanced, recurrent, or ...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-006-9035-2
更新日期:2006-11-01 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
pub_type: 杂志文章
doi:10.1007/s10637-017-0559-4
更新日期:2018-10-01 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
pub_type: 杂志文章
doi:10.1023/a:1006206814025
更新日期:1998-01-01 00:00:00
abstract:BACKGROUND:Dacomitinib (PF-00299804) is an oral, irreversible, small molecule inhibitor of human epidermal growth factor receptor-1, -2, and -4 tyrosine kinases. METHODS:This phase I, open-label, dose-escalation study (clinicaltrials.gov: NCT00783328) primarily evaluated the safety and tolerability of dacomitinib by d...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-011-9789-z
更新日期:2012-12-01 00:00:00
abstract::We investigated proliferation and apoptosis induction in Jurkat T-leukemia cells by the new isothiocyanate 4-(methylthio)butylisothiocyanate (MTBITC). To help elucidate whether the effects of MTBITC are specific for cancer cells, we tested MTBITC on freshly isolated, non-transformed human peripheral T lymphocytes. The...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1023/B:DRUG.0000011788.19754.54
更新日期:2004-04-01 00:00:00
abstract::Six patients with incurable malignancies were originally treated with vitamin E, 3200 IU/day for fourteen days, followed by the same dose of vitamin E daily plus LCV (20 mg/m2 i.v. bolus daily x 5) with 5FU (425 mg/m2 i.v. bolus immediately following LCV). The same schedule of LCV and 5FU was repeated 4 weeks later, t...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
doi:10.1023/a:1006484031959
更新日期:2001-01-01 00:00:00
abstract::Fourteen patients with acute leukemia in relapse were treated with difluoromethylornithine (DFMO) alone or in combination with methylglyoxal-bis(guanylhydrazone) (MGBG) as part of Phase I studies. Five patients included in the trial exhibited morphologic evidence of cellular differentiation during the course of treatm...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/BF00170848
更新日期:1989-07-01 00:00:00
abstract::Hepatocellular carcinoma (HCC) is the most prevalent type of tumor among primary liver tumors and is the second highest cause of cancer-related deaths worldwide. Current therapies are controversial, and more research is needed to identify effective treatments. A new synthetic compound, potassium 5-cyano-4-methyl-6-oxo...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-020-00941-2
更新日期:2020-12-01 00:00:00
abstract::Nafazatrom was tested against a variety of human malignancies with the human tumor stem cell assay at one or more of the following concentrations: 1, 10, 25, and 100 micrograms/ml X 1 h or 0.05, 0.5, or 5 micrograms/ml by continuous exposure. Major (greater than or equal to 70%) inhibition was noted in 7/52 adenocarci...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/BF00173781
更新日期:1984-01-01 00:00:00
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
更新日期:2011-08-01 00:00:00
abstract::Posterior reversible encephalopathy syndrome (PRES) is a clinical/radiological syndrome characterized by symptoms that can include seizure, headache, impaired vision and hypertension, and can be confirmed by magnetic resonance imaging. Numerous reports have emerged that describe PRES in cancer patients. The list of me...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-014-0193-3
更新日期:2015-06-01 00:00:00
abstract::Over forty papers describing correlations between in vitro human tumor sensitivity to a variety of chemotherapeutic agents and the in vivo response of patients to those agents have been published since the publication in 1978 by Salmon and Hamburger of their results of a human tumor colony-forming chemosensitivity ass...
journal_title:Investigational new drugs
pub_type: 杂志文章,评审
doi:10.1007/BF00173788
更新日期:1984-01-01 00:00:00
abstract::Glioblastoma is a fast-growing primary brain tumor observed in adults with the worst prognosis. Preclinical studies have demonstrated the encouraging anticancer activity of statins. This study evaluated the efficacy of atorvastatin in combination with standard therapy in patients with glioblastoma. In this prospective...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-020-00992-5
更新日期:2020-08-27 00:00:00
abstract::Antiprogestins have been largely utilized in reproductive medicine, yet their repositioning for oncologic use is rapidly emerging. In this study we investigated the molecular mediators of the anti-ovarian cancer activity of the structurally related antiprogestins RU-38486, ORG-31710 and CDB-2914. We studied the respon...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-011-9655-z
更新日期:2012-06-01 00:00:00
abstract::This study was designed to test the hypothesis that specific inhibition of cathepsins B and L will cause death of neuroblastoma cells. Five compounds that differ in mode and rate of inhibition of these two enzymes were all shown to cause neuroblastoma cell death. Efficacy of the different compounds was related to thei...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-012-9826-6
更新日期:2013-02-01 00:00:00
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
更新日期:2017-04-01 00:00:00
abstract::VEGF signaling through VEGFR-2 is the major factor in glioblastoma angiogenesis. CT-322, a pegylated protein engineered from the 10th type III human fibronectin domain, binds the VEGFR-2 extracellular domain with high specificity and affinity to block VEGF-induced VEGFR-2 signaling. This study evaluated CT-322 in an o...
journal_title:Investigational new drugs
pub_type: 杂志文章,随机对照试验
doi:10.1007/s10637-014-0186-2
更新日期:2015-02-01 00:00:00
abstract::Cyclophosphamide (CPA) is widely used against leukemic and lymphoproliferative diseases, but in vitro studies on response to this agent so far have been limited to instable derivatives with poor galenic properties. ASTA Z 7557 is a newly synthesized "activated cyclophosphamide" that circumvents the need for hepatic ac...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/BF00232346
更新日期:1984-01-01 00:00:00