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 synergistic anti-metastatic efficacy of a combination of sorafenib (SF), a multi-kinase inhibitor, and β-ionone (BI), a precursor of carotenoids. We found that SF (1 μM) in combination with BI (1 μM) synergistically inhibited cell invasion and additively inhibited cell migration, especially at 48 h of incubation. Mechanistically, the combination of SF and BI was found to decrease the protein expression of focal adhesion kinase (FAK) and Rho, and to enhance the protein expression of tissue inhibitor matrix metalloproteinase (TIMP)-1 and TIMP-2. In addition, the combination of SF and BI inhibited the activity of matrix metalloproteinase (MMP)-2 and MMP-9 and decreased the phosphorylation of FAK and of Rac1 proteins. Importantly, SF enhanced the suppressing effect of BI (1-50 μM) on the viability of SK-Hep-1 cells, but not on murine hepatic BNL CL.2 cells, indicating the selective cytotoxicity of this combination on tumor cells. The combination of SF and BI could be a potential therapeutic strategy against human hepatoma cells.
journal_name
Invest New Drugsjournal_title
Investigational new drugsauthors
Huang CS,Lyu SC,Hu MLdoi
10.1007/s10637-011-9727-0subject
Has Abstractpub_date
2012-08-01 00:00:00pages
1449-59issue
4eissn
0167-6997issn
1573-0646journal_volume
30pub_type
杂志文章abstract::Advances in the understanding of the molecular basis for acute myeloid leukemia (AML) have generated new potential targets for treatment. Fms-like tyrosine kinase 3 (FLT3) is one of the most frequently mutated genes in AML and mutations in this gene are associated with poor overall survival. AXL plays a role in the ac...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-017-0470-z
更新日期:2017-10-01 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::L1210 leukemia cells, because of their rapid growth rate in suspension culture and high growth fraction, are ideally suited to screen in vitro for cytotoxic compounds. Although L1210 cells may mimic rapidly growing tumors, they have not been effective in selecting agents active against slow growing solid tumors. We ex...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/BF00175291
更新日期:1987-01-01 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::The modulation of intracellular nuclear factor-kappaB (NF-κB) signaling pathway involved in the deregulated expression of cell proliferation and cell cycle regulatory molecules is a pragmatic approach for chemoprevention. Eugenol (4-allyl-1-hydroxy-2-methoxybenzene), a natural phenolic constituent of oils of cloves is...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-009-9345-2
更新日期:2011-02-01 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::We have recently developed a liposomal nanoparticle (LNP) formulation of irinotecan based on loading method that involves formation of a complex between copper and the water soluble camptothecin. The loading methodology developed for irinotecan was evaluated to develop a LNP topotecan formulation (referred to herein a...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-012-9832-8
更新日期:2013-02-01 00:00:00
abstract::Pharmacological intervention to reduce CRC mortality entails the use of oral agents that can avert carcinogenesis. Silibinin, a major component of silymarin isolated from Silybum marianum (L.) was found to possess attractive remedial features. An in vivo study was designed to elucidate the effect of silibinin on the f...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-009-9237-5
更新日期:2010-06-01 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::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::A novel schedule of 5-fluorouracil administration has been developed for biochemical modulation studies. In combination with the pyrimidine synthesis inhibitor PALA, 5-fluorouracil has been given as a 24-hour infusion, repeated weekly: a dose of 2600 mg/m2 is well tolerated. To identify a suitable dose of 5-fluorourac...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
doi:10.1007/BF00874152
更新日期:1993-05-01 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::Gemcitabine is a nucleoside analogue with excellent clinical activity against solid tumors. Within the cell, gemcitabine is rapidly phosphorylated to its active di- and triphosphate metabolites. Cytotoxicity with gemcitabine appears to be related to multiple effects on DNA replication, where gemcitabine triphosphate c...
journal_title:Investigational new drugs
pub_type: 杂志文章,评审
doi:10.1007/BF00194528
更新日期:1996-01-01 00:00:00
abstract::The purpose of this study was to assess the efficacy and safety of bevacizumab plus cetuximab with or without gemcitabine in patients with advanced pancreatic adenocarcinoma. Patients with locally advanced or metastatic pancreatic adenocarcinoma, previously untreated, were randomized to bevacizumab (10 mg/kg q2w) plus...
journal_title:Investigational new drugs
pub_type: 杂志文章,随机对照试验
doi:10.1007/s10637-011-9691-8
更新日期:2012-08-01 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::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::Chemoprevention opens new perspectives in the prevention of cancer and other degenerative diseases. Use of target-organ biological models at the histological and genetic levels can markedly facilitate the identification of potential chemopreventive agents. Our aim was to study the chemopreventive efficacy of pronyl-ly...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-008-9122-7
更新日期:2008-12-01 00:00:00
abstract::Background To determine the feasibility and efficacy of olanzapine, which is approved by the Pharmaceuticals and Medical Devices Agency as multi acting receptor targeted antipsychotic agent of the thienobenzodiazepine class, for prevention of chemotherapy-induced nausea and vomiting (CINV) in patients undergoing conti...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
doi:10.1007/s10637-017-0487-3
更新日期:2018-02-01 00:00:00
abstract::We have previously described a human pancreatic-ribonuclease variant, named PE5, which carries a non-contiguous extended bipartite nuclear localization signal. This signal comprises residues from at least three regions of the protein. We postulated that the introduction of this signal in the ribonuclease provides it w...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-010-9426-2
更新日期:2011-10-01 00:00:00
abstract::Heparan sulfate mimetics, which we have called the PG500 series, have been developed to target the inhibition of both angiogenesis and heparanase activity. This series extends the technology underpinning PI-88, a mixture of highly sulfated oligosaccharides which reached Phase III clinical development for hepatocellula...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-009-9245-5
更新日期:2010-06-01 00:00:00
abstract::A phase I trial of first-line vorinostat, an orally bio-available histone deacetylase inhibitor, in combination with capecitabine plus cisplatin (XP) was performed to assess recommend phase II trial dose in patients with advanced gastric cancer. Five dose levels of three-weekly vorinostat-XP were tested; vorinostat wa...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-013-9983-2
更新日期:2014-04-01 00:00:00
abstract::Aims A primary objective of this study was to investigate the effect of single and multiple doses of alisertib, an investigational Aurora A kinase inhibitor, on the QTc interval in patients with advanced malignancies. The dose regimen used was the maximum tolerated dose which was also the recommended phase 3 dose (50 ...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-017-0498-0
更新日期:2018-04-01 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::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::As HER2 is a client protein of the molecular chaperone Hsp90, targeting Hsp90 may be beneficial in HER2-positive breast cancer. In this study, the activity of the Hsp90 inhibitor NVP-AUY922 was assessed in HER2 overexpressing breast cancer cell lines, including two cell line models of acquired trastuzumab-resistance. ...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-017-0556-7
更新日期:2018-08-01 00:00:00
abstract::3-Deazaguanine (Dezaguanine), a purine antimetabolite, was evaluated in a phase I trial in 42 patients with advanced solid tumors. Dezaguanine was given as a weekly intravenous infusion for three consecutive weeks of a four-week cycle. The dose ranged from 30 to 2000 mg/m2; no consistent dose-limiting hematologic or g...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
doi:10.1007/BF00198593
更新日期:1990-11-01 00:00:00
abstract:PURPOSE:To assess the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), safety, and tolerability of MN-209, a novel vascular disrupting agent, in patients with advanced solid tumors. STUDY DESIGN:MN-029 was administered weekly for three consecutive weeks out of four; two cycles were planned. Dose escalation ...
journal_title:Investigational new drugs
pub_type: 杂志文章,多中心研究
doi:10.1007/s10637-009-9264-2
更新日期:2010-08-01 00:00:00
abstract::Thirty-three patients with advanced colorectal carcinoma were entered on a phase II trial of weekly IV aminothiadiazole (175 mg/m2 escalated to 200 mg/m2) with concomitant allopurinol and non-steroidal anti-inflammatory agents (NSAID's). Toxicity was predominantly GI, cutaneous, and chest pain/dyspnea. Twenty-five per...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
doi:10.1007/BF00873044
更新日期:1994-01-01 00:00:00
abstract::Twenty-four evaluable patients with epithelial ovarian cancer resistant to primary therapy, or relapsing after response to initial therapy, were treated with acivicin utilizing a daily X 5 schedule. One patient achieved a partial response lasting five months; the remaining 23 patients showed no objective response. Pro...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/BF00172016
更新日期:1986-01-01 00:00:00
abstract::Twenty-four patients with advanced epidermoid carcinoma of the esophagus were treated with trimetrexate (TMTX), a lipid soluble non-classical antifol. Patients were given TMTX 8 mg/m2 intravenously day 1-5 every 28 days. In nine of these patients the dose was escalated to 12 mg/m2 day 1-5 every 28 days. Three patients...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/BF00173651
更新日期:1988-12-01 00:00:00