Abstract:
:Linking chemotherapeutic drugs to a macromolecular carrier system may enhance tumor targeting, reduce toxicity and overcome drug resistance mechanisms. As an elementary model to evaluate the pharmacological properties of macromolecular drug carrier systems we chose rat serum albumin (RSA) for carrier and methotrexate (MTX) as antineoplastic drug. The conjugation procedure yielded conjugates with an approximate 1:1 molar loading rate (MTX(1)-RSA). In the first part of the study a residualizing [111In]DTPA protein label was used for mapping in vivo the catabolic sites of the native carrier protein and of the MTX(1)-RSA drug conjugate in Walker 256 carcinosarcoma bearing rats. The tumor accumulation was about 14% of the injected dose for the RSA and MTX(1)-RSA tracers after 24 h. Tracer entrapment by organs with an active mononuclear phagocyte system was low (liver below 7% and spleen below 1.5% of the injected dose after 24 h). The 1:1 conjugation of MTX to RSA did not decisively alter the pharmacokinetic properties nor the tumor or tissue distribution of the native carrier protein RSA. In the second part of the study the different properties of the MTX(1)-RSA conjugate were compared with MTX in vivo. About 2 mg MTX/kg body weight either of the drug conjugate or of the original drug were injected after being additionally spiked with radiolabeled tracers. Plasma concentrations were simultaneously determined by immunological and radioactive means. After 24 h about 12% MTX(1)-RSA was found in circulation compared to 0.03% MTX. Favorable tumor accumulation rates of about 14% were achieved for MTX(1)-RSA versus 0.04% for MTX. About 45-fold more of the injected dose of [3H]MTX accumulated in the liver as compared to the tumor (1.5 versus 0.03%) after 24 h. Conjugation of MTX to RSA reversed this ratio in favor of the tumor to 1:1.4 (13.6 versus 9.6%). In conclusion, the potential therapeutic benefit of the MTX(1)-RSA conjugate lies in its very long tumor exposure time and its improved tumor accumulation rate compared to conventional MTX. In addition the conjugation to albumin might enhance the therapeutic effects over those achieved by long-term continuous infusion of MTX, as MTX(1)-RSA enters the cells by a different uptake mechanism. This might also help to circumvent MTX resistance mechanisms, such as a reduction in folate receptor numbers or impaired MTX polyglutamylation.
journal_name
Anticancer Drugsjournal_title
Anti-cancer drugsauthors
Stehle G,Wunder A,Sinn H,Schrenk HH,Schütt S,Frei E,Hartung G,Maier-Borst W,Heene DLdoi
10.1097/00001813-199710000-00004subject
Has Abstractpub_date
1997-10-01 00:00:00pages
835-44issue
9eissn
0959-4973issn
1473-5741journal_volume
8pub_type
杂志文章abstract::Alpha-tocopheryloxy acetic acid (α-TEA) is an ether derivative of vitamin E and has been shown to suppress tumor growth in various murine and human xenograft tumor models, including melanoma, breast, lung, prostate, and ovarian cancers. The purpose of this study was to assess its safety and pharmacokinetics after repe...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e32834f6271
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abstract::PC cell-derived growth factor is a novel growth factor for tumor formation and progression. No comprehensive literature concerning PC cell-derived growth factor expression status and its biological function in squamous cell carcinoma, especially in the larynx, is, however, available. The target of this study is to eva...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/01.cad.0000236315.96574.58
更新日期:2007-01-01 00:00:00
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journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e32835a4dac
更新日期:2013-02-01 00:00:00
abstract::The clinical development of combinations of cisplatin or carboplatin with DNA topoisomerase I (Topo I) inhibitors is based on their overlapping spectrum of antitumor activity and their in vitro synergy, but is limited by significant hematotoxicity. We studied the cellular interactions between oxaliplatin and topotecan...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199902000-00008
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abstract::In our institution, 103 glioblastoma multiforme (GBM) patients aged from 55 to 83 years were treated since November 1994 as follows. All patients underwent surgical intervention (gross total resection, n = 35; subtotal resection, n = 38; stereotactic biopsy, n = 30). Subsequently all patients were offered radiotherapy...
journal_title:Anti-cancer drugs
pub_type: 临床试验,杂志文章
doi:10.1097/00001813-200302000-00007
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abstract::A new dosage format, cisplatin microcrystals suspended in oil (CDDP-oil), was developed for the treatment of peritoneal carcinomatoses. We studied the acute toxicity of CDDP-oil injected intraperitoneally in mice. The 50% lethal dose was 30.3 mg/kg (27.1-33.7 mg/kg at the 95% confidence level), which was 1.79 times th...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199306000-00015
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abstract::Cantharidin is a natural toxin that possesses potent anti-tumor properties. Its clinical application, however, is limited due to severe side-effects. Its cytotoxicity is believed to be mediated by the inhibition of serine/threonine protein phosphatase 2A. In order to identify new compounds with potential clinical ther...
journal_title:Anti-cancer drugs
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doi:10.1097/01.cad.0000217428.90325.35
更新日期:2006-09-01 00:00:00
abstract::There is limited evidence on the costs associated with ipilimumab. We investigated healthcare costs of all Dutch patients with advanced cutaneous melanoma who were treated with ipilimumab. Data were retrieved from the nation-wide Dutch Melanoma Treatment Registry. Costs were determined by applying unit costs to indivi...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000628
更新日期:2018-07-01 00:00:00
abstract::BPR0C305 is a novel N-substituted indolyl glyoxylamide previously reported with in-vitro cytotoxic activity against a panel of human cancer cells including P-gp-expressing multiple drug-resistant cell sublines. The present study further examined the underlying molecular mechanism of anticancer action and evaluated the...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000014
更新日期:2013-11-01 00:00:00
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journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:
更新日期:1996-02-01 00:00:00
abstract::We examined the anti-tumor activity and structure-activity requirements of omega-hydroxy fatty acids (omega-HFAs) on the human melanoma cell line G361. The omega-hydroxystearic acid (omega-HSA) had strong growth-inhibiting and cytotoxic activity. Although omega-hydroxypalmitic acid (omega-HPA) also had growth-inhibiti...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-200506000-00010
更新日期:2005-06-01 00:00:00
abstract::Multidrug resistance (MDR) is a major obstacle to successful chemotherapy for cancer; thus, novel MDR reversers are urgently needed. In the present study, we assessed whether two synthetic derivatives of 23-hydroxybetulinic acid, 3,23-O-diacetyl-17-1,4'-bipiperidinyl betulinic amide (DABB) and 3,23-O-dihydroxy-17-1,4'...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e32835fcc77
更新日期:2013-06-01 00:00:00
abstract::Tolerability and response rate to weekly combination chemotherapy with trastuzumab and vinorelbine in Japanese women with HER2-overexpressing breast cancer not previously receiving either therapy were assessed. Tumor response was evaluated every 4 weeks and adverse events were graded. A total of 23 patients from six p...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,多中心研究
doi:10.1097/CAD.0b013e328302eb15
更新日期:2008-08-01 00:00:00
abstract::Colchicine, the main alkaloid of the poisonous plant meadow saffron (Colchicum autumnale L.), is a classical drug used for the treatment of gout and familial Mediterranean fever. Although colchicine is not clinically used to treat cancer because of toxicity, it exerts antiproliferative effects through the inhibition o...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:10.1097/CAD.0000000000000464
更新日期:2017-03-01 00:00:00
abstract::We report Guillain-Barre syndrome (GBS), developed in a patient with metastatic colon cancer, receiving oxaliplatin-based chemotherapy. The 53-year-old patient was treated with first-line chemotherapy consisting of oxaliplatin 45 mg/m2, 5-fluorouracil 450 mg/m2 and folinic acid 200 mg/m2, all given on the same day in ...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-200411000-00010
更新日期:2004-11-01 00:00:00
abstract::Lung cancer remains the leading cause of cancer-associated mortality in China and the world. Increasing numbers of studies have reported that sphingosine kinase 1 (SPK1) is frequently highly expressed in tumors of various origins, including lung cancer, and its high expression contributes toward tumor progression. How...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000733
更新日期:2019-06-01 00:00:00
abstract::A combined treatment with conventional chemotherapies can enhance the effectiveness of chemotherapeutic agents against cancers. Here, we have shown that the naturally occurring triterpenoids synergistically enhance the response of cervical cancer cells to taxol. Of the triterpenoid compounds, pristimerin enhanced the ...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e328347181a
更新日期:2011-09-01 00:00:00
abstract::Dihydroartemisinin (DHA), a semisynthetic derivative of artemisinin, has recently shown antitumor activity in various cancer cells. Its effect on pancreatic cancer is, however, unknown and the mechanism is unclear. The study aims to investigate its antitumor activity and underlying mechanisms in human pancreatic cance...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e3283212ade
更新日期:2009-02-01 00:00:00
abstract::The efficacy of chemotherapy for advanced gastric cancer with palliative intent compared with supportive care alone is now widely accepted. However, the best choice of chemotherapy regimen for patients with advanced gastric cancer is still a matter of controversy and requires further investigation. This study is perfo...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e3283273509
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abstract::Combretastatin A4 phosphate (CA4P) is a water-soluble prodrug of combretastatin A4 (CA4). The vascular targeting agent CA4 is a microtubule depolymerizing agent. The mechanism of action of the drug is thought to involve the binding of CA4 to tubulin leading to cytoskeletal and then morphological changes in endothelial...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:10.1097/00001813-200403000-00001
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journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000170
更新日期:2015-01-01 00:00:00
abstract::We have previously shown that L-methionine inhibits proliferation of breast, prostate, and colon cancer cells. This study extends these findings to BXPC-3 (mutated p53) and HPAC (wild-type p53) pancreatic cancer cells and explores the reversibility of these effects. Cells were exposed to L-methionine (5 mg/ml) for 7 d...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000038
更新日期:2014-02-01 00:00:00
abstract::The main aim of this study was to establish a novel paclitaxel (PTX)-resistant human gastric carcinoma cell line and to investigate its biological significance. A cell line, MGC803/PTX, was established by gradually increasing PTX density on the basis of MGC803 over a period of 10 months. In addition, a pair of resista...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000601
更新日期:2018-07-01 00:00:00
abstract::Isoquercitrin isolated from the aerial parts of Hyptis fasciculata was evaluated according to its capacity to interfere with glioblastoma (Gbm) cell growth. Gbm cells were incubated with isoquercitrin, quercetin, or rutin at concentrations of 25, 50, and 100 mumol/l for 24, 48, and 72 h. Quercetin and rutin affected G...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e32832d1149
更新日期:2009-08-01 00:00:00
abstract::Mantle cell lymphoma (MCL) remains incurable for most patients, and proteasome inhibitors like bortezomib induce responses in a minority of patients with relapsed disease. Fenretinide is a retinoid that has shown preclinical activity in B-cell lymphomas. We hypothesized that these agents could yield augmented antitumo...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000274
更新日期:2015-10-01 00:00:00
abstract::Macroautophagy (hereafter referred to as autophagy) plays essential roles in cellular and organismal homeostasis. Transcription factor EB (TFEB) is a master regulator of autophagy and lysosome biogenesis. It is not fully understood how the function of TFEB in autophagy pathway is regulated. Here, we show that Rac1 GTP...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000816
更新日期:2019-11-01 00:00:00
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journal_title:Anti-cancer drugs
pub_type: 临床试验,杂志文章
doi:10.1097/00001813-199904000-00003
更新日期:1999-04-01 00:00:00
abstract::In a previous study, we showed that a combination of an oral fluoropyrimidine anticancer agent (S-1) and gemcitabine (GEM) had synergistic effects on cell growth and cell cycle arrest in the pancreatic cancer cell line MIA PaCa-2. Therefore, we conducted further mechanistic studies using the pancreatic cancer cell lin...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e328350e8c7
更新日期:2012-06-01 00:00:00
abstract::Antibody-cytokine fusion proteins (also called 'immunocytokines') represent an emerging class of biopharmaceutical products, which are being considered for cancer immunotherapy. When used as single agents, pro-inflammatory immunocytokines are rarely capable of inducing complete and durable cancer regression in mouse m...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000938
更新日期:2020-09-01 00:00:00
abstract::Metformin, an oral antidiabetic agent, has been reported to potentiate chemotherapeutic-induced cytotoxicity. In this study, we investigated the effects and molecular mechanisms of metformin in sensitizing tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in human bladder cancer cells. ...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000116
更新日期:2014-09-01 00:00:00