Abstract:
:Compared to doxorubicin, equimolar epirubicin toxicity is reduced by about 50% by the epimerization of a hydrogen and hydroxyl group at the 4' position of the anthracycline sugar moiety. The circadian timing of doxorubicin administration markedly affects its lethal and sub-lethal bone marrow and gut toxicities in mice, as well as the severity of its clinical toxicity. We tested whether the timing of administration of equitoxic epirubicin doses similarly affected the toxicological response in female CD2F1 mice. A large and highly reproducible effect of the circadian stage of administration was documented with best drug tolerance occurring during the first half of the daily rest (light) span of the animals. In addition to this circadian rhythm, a significant seasonal effect was found with significantly fewer deaths occurring after epirubicin was given in the Summer, as compared to the Winter. Safest circadian timing for epirubicin is statistically significantly earlier in the day than for doxorubicin, while their seasonal patterns are quite similar.
journal_name
Invest New Drugsjournal_title
Investigational new drugsauthors
Mormont MC,von Roemeling R,Sothern RB,Berestka JS,Langevin TR,Wick M,Hrushesky WJdoi
10.1007/BF00173645subject
Has Abstractpub_date
1988-12-01 00:00:00pages
273-83issue
4eissn
0167-6997issn
1573-0646journal_volume
6pub_type
杂志文章abstract::A retrospective cohort study was performed to investigate the effectiveness of preemptive postsurgical therapy with cetuximab for patients with a major risk of recurrence or metastasis after clinical complete resection of primary oral squamous cell carcinoma (OSCC). The study period was from 2007 to 2019 for patients ...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-021-01062-0
更新日期:2021-01-15 00:00:00
abstract::The anti-tumor properties of novel derivatives prepared from Aconitum C(20)-diterpenoid alkaloid, which show the least toxicity among the Aconitum alkaloids, were investigated in the Non-Hodgkin's lymphoma cell line Raji cells. Two novel Aconitum C(20)-diterpenoid alkaloid derivatives, 11-m-Trifluorometylbenzoyl (Mb)-...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-009-9327-4
更新日期:2011-02-01 00:00:00
abstract::An inflammatory myofibroblastic tumor (IMT) is a rare invasive soft tissue mass with intramuscular penetration that is primarily treated via a surgical procedure. However, with unclear boundaries and a high rate of relapse, there is no standard treatment for recurrence or unresectable tumors. It is noteworthy that app...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-020-00984-5
更新日期:2020-09-11 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::Bombesin/gastrin-releasing peptides (BN/GRP) were shown to bind selectively to cell surface receptors, stimulating the growth of various types of malignancies in murine and human models. The novel BN/GRP synthetic receptor antagonist, RC-3095, was able to produce long-lasting tumor regressions in murine and human tumo...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-006-6886-5
更新日期:2006-09-01 00:00:00
abstract::Tea (Camellia sinensis) is one of the most widely used beverages worldwide and tea consumption has been shown to have an inverse correlation to the incidence of human cancers in epidemiological and experimental studies. In the present study, the protective effects of green tea polyphenols (GTP) and black tea polypheno...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-008-9204-6
更新日期:2009-12-01 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::Interleukin-4 is a highly pleiotropic T-cell derived lymphokine that has been reported to stimulate a host cell-mediated antitumor response. Recombinant human interleukin-4 (rhuIL-4) is currently undergoing clinical phase I trials. We have studied the growth modulating effects of rhuIL-4 on a variety of freshly explan...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/BF00944180
更新日期:1992-11-01 00:00:00
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::Background This first-in-human phase 1 study assessed the safety of TAS-114, a novel deoxyuridine triphosphatase inhibitor, combined with S-1 to determine its maximum tolerated dose (MTD) and recommended dose (RD). Methods In this dose-escalation study with a 3 + 3 design, TAS-114 and S-1 were concurrently administere...
journal_title:Investigational new drugs
pub_type: 杂志文章,多中心研究
doi:10.1007/s10637-018-0697-3
更新日期:2019-06-01 00:00:00
abstract::Sixteen patients with stage IV melanoma, who were heavily pretreated, received 11 mg/m2/day of intravenous Irofulven for five consecutive days every 28 days. There were no objective tumor responses, although one patient exhibited stable disease after 4 cycles. The most common toxicities were grade 1/2 nausea, vomiting...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
doi:10.1023/a:1016261918256
更新日期:2002-08-01 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::The novel oral antiangiogenic agent TSU-68 was investigated in patients with metastatic breast cancer. Patients with anthracycline-pretreated metastatic breast cancer were randomly assigned to receive either TSU-68 400 mg twice daily on days 1-21 plus docetaxel 60 mg/m(2) on day 1 every 3 weeks, or docetaxel 60 mg/m(2...
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/s10637-014-0093-6
更新日期:2014-08-01 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::Menogaril, a semisynthetic anthracycline antibiotic, was administered to patients with metastatic adenocarcinoma of the prostate. Forty-five patients with measurable disease and 45 patients with evaluable disease received 150-200 mg/m2 over 1 hour every 28 days. There were three partial responses (PR) among 87 patient...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1007/BF00873240
更新日期:1994-01-01 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::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: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::The protective role of Luteolin (LUT) against Azoxymethane (AOM)-induced mouse colon carcinogenesis has been documented earlier. The aim of this study is to investigate on the mechanism of chemopreventive action exhibited by LUT employing AOM-induced colon carcinogenesis in mice as an experimental model. LUT inhibited...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-009-9359-9
更新日期:2011-04-01 00:00:00
abstract::T cells are important effectors in anti-tumor immunity, and aberrant expression of B7 family members may contribute to tumor evasion. In this study, we analyzed expression of costimulatory molecules on human hematologic tumor cells and explored whether B7-H3, a member of the B7 superfamily, is an effective target for ...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-019-00819-y
更新日期:2020-06-01 00:00:00
abstract::Anthracycline antibiotics (ANT), such as doxorubicin or daunorubicin, are a class of anticancer drugs that are widely used in oncology. Although highly effective in cancer therapy, their usefulness is greatly limited by their cardiotoxicity. Possible mechanisms of ANT cardiotoxicity include their conversion to seconda...
journal_title:Investigational new drugs
pub_type: 杂志文章,评审
doi:10.1007/s10637-017-0443-2
更新日期:2017-06-01 00:00:00
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 c...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-010-9390-x
更新日期:2011-08-01 00:00:00
abstract::Capecitabine (N4-pentyloxycarbonyl-5'-deoxy-5-fluorocytidine) is a novel fluoropyrimidine carbamate, which was designed to be sequentially converted to 5-fluorouracil (5-FU) by three enzymes located in the liver and in tumors; the final step is the conversion of 5'-deoxy-5-fluorouridine (5'-DFUR) to 5-FU by thymidine ...
journal_title:Investigational new drugs
pub_type: 杂志文章,评审
doi:10.1023/a:1006497231579
更新日期:2000-11-01 00:00:00
abstract::We studied the effect of riccardin D, a macrocyclic bisbibenzyl, which was isolated from the Chinese liverwort plant, on human leukemia cells and the underlying molecular mechanism. Riccardin D had a significant antiproliferative effect on human leukemia cell lines HL-60, K562 and its multidrug resistant (MDR) counter...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-010-9554-8
更新日期:2012-02-01 00:00:00
abstract::The novel compound N-benzoxazol-2-yl-N'-1-(isoquinolin-3-yl-ethylidene)-hydrazine (EPH136) has been shown to exhibit antitumor activity in vitro and in vivo. A COMPARE analysis showed that the patterns of cellular effects of EPH136 are not related to any of 175 standard antitumor agents with a known mechanism of actio...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-008-9156-x
更新日期:2009-06-01 00:00:00
abstract::N-(phosphonacetyl)-disodium L-aspartic acid (PALA) demonstrates a synergistic antitumor effect when combined with 5-Fluorouracil (5-FU) in in vitro studies. In a Phase II trial, 23 eligible patients with unresectable or metastatic adenocarcinoma of the stomach were treated with weekly i.v. bolus PALA (250 mg/M2) follo...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
doi:10.1007/BF00180821
更新日期:1996-01-01 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::Monoclonal antibodies directed against the immune checkpoint protein cytotoxic T-lymphocyte antigen-4 (CTLA-4; CD152) have been investigated in metastatic melanoma and other cancers and have shown promising results. Inhibition of CTLA-4 characteristically induces well-known side effects called "immune-related adverse ...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-014-0092-7
更新日期:2014-08-01 00:00:00
abstract::A Phase II study of Didemnin-B, a marine cyclic depsipeptide, was undertaken in patients with progressive epithelial ovarian cancer. The starting dose was 2.6 mg/m2. Fifteen patients received the drug, of whom twelve were evaluable. There were no responses observed in the twelve patients. The two most frequent toxicit...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
doi:10.1007/BF01275473
更新日期:1992-04-01 00:00:00
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