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 that RX871024, but not another insulinotropic imidazoline compound (BL11282), suppressed AMPK activity in MIN6 cells. The inhibitory effect of RX871024 on AMPK was supported by the observation that the imidazoline induced lipid droplet formation in the cytoplasm of MIN6 cells. This reflects stimulation of anabolic pathways and inhibition of catabolic pathways in the cell that happen under conditions when AMPK is inhibited. Activation of AMPK by 5-aminoimidazole-4-carboxamide riboside (AICAR) elevated basal and cytokine-induced death in primary β-cells and in insulinoma MIN6 cells. RX871024 aggravated AICAR-induced insulinoma MIN6 cell death regardless of the presence of pro-inflammatory cytokines. The specific cytotoxic effect of imidazoline compound RX871024 on insulinoma cell death but not primary β-cell death is independent of its action on AMPK and may suggest the possibility of using this type of compound in the treatment of insulinomas.
journal_name
Invest New Drugsjournal_title
Investigational new drugsauthors
Zaitseva II,Zaitsev SV,Berggren POdoi
10.1007/s10637-016-0362-7subject
Has Abstractpub_date
2016-08-01 00:00:00pages
522-9issue
4eissn
0167-6997issn
1573-0646pii
10.1007/s10637-016-0362-7journal_volume
34pub_type
杂志文章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...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1023/b:drug.0000006170.38419.c9
更新日期:2004-01-01 00:00:00
abstract:BACKGROUND:Gemcitabine is a pro-drug that has to be phosphorylated to gemcitabine-triphosphate in order to exhibit its antineoplastic activity. This reaction involves the enzyme deoxycytidine kinase which is saturated at plasma concentrations following standard 30-min infusions. Pharmacological studies indicate that pr...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
doi:10.1007/s10637-005-5859-4
更新日期:2005-03-01 00:00:00
abstract::Myricetin is a naturally omnipresent benzo-α-pyrone flavonoids derivative; has potent anticancer activity. Receptor tyrosine kinases family provides the decisive role in cancer initiation and progression. These receptors have recently caught the attention of the researchers as an attractive target to combat cancer, ow...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-015-0240-8
更新日期:2015-06-01 00:00:00
abstract::This report shows that N-acylation of the protein kinase C (PKC) substrate Arg-Lys-Arg-Thr-Leu-Arg-Arg-Leu (RKRTLRRL) provides it with a potent inhibitory activity against PKC. N-myristoyl-RKRTLRRL inhibited Ca2(+)- and phosphatidylserine (PS)-dependent histone phosphorylation catalyzed by PKC with a 50% inhibitory co...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/BF00175084
更新日期:1991-05-01 00:00:00
abstract::Estrogens play a central role in reproductive physiology. The cellular effects of estrogens are mediated by binding to nuclear receptors (ER) which activate transcription of genes involved in cellular growth control. At least two such receptors, designated ERalpha and ERbeta, mediate these effects in conjunction with ...
journal_title:Investigational new drugs
pub_type: 杂志文章,评审
doi:10.1023/a:1006348907994
更新日期:1999-01-01 00:00:00
abstract::Chaetoglobosin K (ChK) is a natural product that inhibits anchorage-dependent and anchorage-independent growth of ras-transformed cells, prevents tumor-promoter disruption of cell-cell communication, and reduces Akt activation in tumorigenic cells. This study demonstrates how ChK modulates the JNK pathway in ras-trans...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-012-9883-x
更新日期:2013-06-01 00:00:00
abstract::Breast cancer is commonly treated with anti-estrogens or aromatase inhibitors, but resistant disease eventually develops and new therapies for such resistance are of great interest. We have previously isolated several tamoxifen-resistant variant sub-lines of the MCF-7 breast cancer cell line and provided evidence that...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-011-9768-4
更新日期:2012-12-01 00:00:00
abstract::Background High-risk neuroblastoma has poor outcomes with high rates of relapse despite aggressive treatment, and novel therapies are needed to improve these outcomes. Ponatinib is a multi-tyrosine kinase inhibitor that targets many pathways implicated in neuroblastoma pathogenesis. We hypothesized that ponatinib woul...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-016-0387-y
更新日期:2016-12-01 00:00:00
abstract:PURPOSE:Cytotoxic and anti-angiogenic drugs are efficacious in malignancies. This trial was undertaken to evaluate the toxicity of a novel regimen combining docetaxel and lenalidomide. PATIENTS AND METHODS:Patients with advanced solid tumors were eligible. Docetaxel was administered on day 1, and lenalidomide was give...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-008-9200-x
更新日期:2009-10-01 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::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::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
pub_type: 杂志文章
doi:10.1007/s10637-014-0132-3
更新日期:2014-10-01 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::Degradation of basement membrane and extracellular matrix by matrix metalloproteinases (MMPs) is believed to be required for tumor invasion, tumor-induced angiogenesis and vascular invasion. A synthetic hydroxamate, batimastat (also known as BB-94), inhibits MMPs by binding the zinc ion in the active site of the MMP. ...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
doi:10.1007/BF00210790
更新日期:1996-01-01 00:00:00
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
更新日期:2013-12-01 00:00:00
abstract::Fifty-four evaluable patients with SCLC previously treated with chemotherapy received either N-methylformamide or spirogermanium. There was one partial response to N-methylformamide. The median survival times for patients treated with N-MF and spirogermanium were 11.7 and 12.6 weeks respectively. Five patients treated...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
doi:10.1007/BF00177255
更新日期:1990-05-01 00:00:00
abstract:PURPOSE:To investigate the hypothesis that a systemic agent designed to inhibit dihydropyrimidine dehydrogenase (DPD), the first enzyme in the fluoropyrimidine degradative pathway, could improve the effective amount of 5-fluorouracil (5-FU) delivered to a tumor resulting in enhanced response. PATIENTS AND METHODS:Elig...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1023/a:1020662113061
更新日期:2002-11-01 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
pub_type: 杂志文章
doi:10.1007/BF00175378
更新日期:1984-01-01 00:00:00
abstract::CP-4126 is a gemcitabine (2',2'-difluorodeoxycytidine; dFdC) 5' elaidic acid ester. The purpose of this dose-escalating study was to assess safety, pharmacokinetics (PK) and preliminary antitumor activity of the oral formulation and to determine the recommended dose (RD) for phase II studies. The study had a two-step ...
journal_title:Investigational new drugs
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1007/s10637-013-9925-z
更新日期:2013-08-01 00:00:00
abstract::Transforming growth factor-beta (TGF-β) signaling pathway plays pivotal roles in various types of cancer. TGF-β receptor 2 (TGFβR2) contains a kinase domain that phosphorylates and activates the downstream of the TGF-β signaling pathway. Our previous microarray analysis revealed marked changes in miR-181a expression i...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-018-0695-5
更新日期:2019-10-01 00:00:00
abstract::Background Treatment of recurrent, unresectable granulosa cell tumor (GCT) of the ovary can be challenging. Given the rarity of the tumor, alternative therapies have been difficult to evaluate in large prospective clinical trials. Currently, to our knowledge, there are no reports of the use of immune checkpoint inhibi...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-020-01043-9
更新日期:2021-01-07 00:00:00
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
更新日期:2017-12-01 00:00:00
abstract::UCN-01 is undergoing Phase I evaluation and is a candidate for combination strategies in the clinic. UCN-01 has been shown to have a variety of effects on cellular targets and the cell cycle. It has also been reported to sensitize cells to several clinical drugs in vitro, possibly in a manner related to p53 status. Th...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1023/a:1006313611677
更新日期:2000-05-01 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: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
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1007/s10637-010-9598-9
更新日期:2012-04-01 00:00:00
abstract::LP-261 is a novel tubulin targeting anticancer agent that binds at the colchicine site on tubulin, inducing G2/M arrest. Screening in the NCI60 cancer cell lines resulted in a mean GI50 of approximately 100 nM. Here, we report the results of testing in multiple mouse xenograft models and angiogenesis assays, along wit...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-010-9520-5
更新日期:2012-02-01 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:TAS-102 is a nucleoside antitumor agent consisting of trifluridine (FTD) and tipiracil hydrochloride (TPI). We investigated the recommended dose (RD) of TAS-102 plus irinotecan for metastatic colorectal cancer refractory to 5-fluorouracil (5-FU) and oxaliplatin. METHODS:This study was used a escalated dose ...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-015-0271-1
更新日期:2015-10-01 00:00:00
abstract::Fourteen patients with active chronic lymphocytic leukemia who had failed prior therapy were treated with progressive doses of weekly intravenous colchicine beginning at 2 mg and escalating as high as 7 mg in a single injection. Responses were seen in two of 14, with a lessening of adenopathy and splenomegaly. Toxicit...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/BF00177418
更新日期:1983-01-01 00:00:00
abstract::Chemotherapy has always been the first therapeutic option for patients with advanced non-small cell lung cancer (NSCLC) with untreatable oncogenic mutations. However, chemotherapy has demonstrated limited success and is associated with severe side effects. This research aimed to investigate the antitumor efficacy and ...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-019-00876-3
更新日期:2020-08-01 00:00:00