Abstract:
:Although the combination of cisplatin and etoposide has been used as standard therapy for small-cell lung cancer, it is difficult to demonstrate combination effects between cisplatin and etoposide in vitro. We therefore adopted a 3-dimensional (3-D) model to analyze the combination effects of anticancer drugs, and compared the results of analysis by the new 3-D model with those obtained from traditional 2-D models for the cisplatin-etoposide combination. In this study, using a human small-cell lung-cancer cell line (SBC-3), 3-D model analysis clearly identified a relationship depending on the concentrations of both drugs, and demonstrated that peak synergy occurred at the higher concentrations of cisplatin and etoposide. Antagonistic interactions were noted with a nadir at low concentrations of etoposide and cisplatin. In contrast, 2-D models such as combination index and isobologam analysis fail to characterize the complex interactions between cisplatin and etoposide, since their joint effects are concentration-dependent. Combination index (CI) plots show that synergy is evident only for molar ratios of cisplatin: etoposide of 2:1 to 1:5. On isobologram analysis, synergy could be detected when great inhibitory effects on cell growth were present (high endpoint), but not with small inhibitory effects (lower endpoints). Thus, either synergy or antagonism may occur, but depend on the selection of variables, such as the molar ratios or the endpoints chosen for the experiments. This could explain the inconsistency in the in vitro combination effects reported to date. The 3-D model, which compensates for the above deficiencies of 2-D models, can facilitate rigorous analysis of drug interactions over the entire clinical dose range, using microcomputers and sophisticated graphics programs. This direct and pragmatic method offers investigators a practical new tool with which to analyze drug combinations for cancer chemotherapy.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
Kanzawa F,Nishio K,Fukuoka K,Fukuda M,Kunimoto T,Saijo Ndoi
10.1002/(sici)1097-0215(19970502)71:3<311::aid-ijcsubject
Has Abstractpub_date
1997-05-02 00:00:00pages
311-9issue
3eissn
0020-7136issn
1097-0215pii
10.1002/(SICI)1097-0215(19970502)71:3<311::AID-IJCjournal_volume
71pub_type
杂志文章abstract::The topic of this review is the role of stromal-epithelial interactions in normal and malignant prostatic growth. Because cell-cell interactions and androgens play such key roles in the prostate, the goal of this review will be to apply endocrinologic and developmental concepts to the understanding of normal and malig...
journal_title:International journal of cancer
pub_type: 杂志文章,评审
doi:10.1002/ijc.11335
更新日期:2003-10-20 00:00:00
abstract::The association of fruit and vegetable consumption and lung cancer incidence was evaluated using the most recent data from the European Prospective Investigation into Cancer and Nutrition (EPIC), applying a refined statistical approach (calibration) to account for measurement error potentially introduced by using food...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.22807
更新日期:2007-09-01 00:00:00
abstract::The targeted radiotherapy of neuroblastoma with 131l-labelled metaiodobenzyl guanidine (mIBG) is now the subject of several clinical studies. The precise intracellular localization of mIBG, necessary for nuclear microdosimetry, has not previously been described. We report the use of electron-energy-loss spectroscopy a...
journal_title:International journal of cancer
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doi:10.1002/ijc.2910470615
更新日期:1991-04-01 00:00:00
abstract::The mismatch repair (MMR) genes are involved in the maintenance of genomic integrity. Recently, we showed that common variants in these genes are unlikely to contribute significantly to colorectal cancer risk. The aim of this study was to investigate the role of common variants in the mismatch repair pathway as progno...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.24120
更新日期:2009-04-15 00:00:00
abstract::Powerful analytical tools are vital for characterizing the complex molecular changes underlying oncogenesis and cancer treatment. This is particularly true, if information is to be collected in vivo by noninvasive approaches. In the recent past, hyperpolarized (13)C magnetic resonance (MR) spectroscopy has been employ...
journal_title:International journal of cancer
pub_type: 杂志文章
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abstract::The heterogeneous nuclear ribonucleoprotein (hnRNP) K is an essential RNA and DNA binding protein involved in gene expression and signal transduction including DNA transcription, RNA splicing, RNA stability and translation. The role of hnRNP K in cancer is relatively understudied. However, several cellular functions s...
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abstract::Treatment of lung cancer is often performed with cone-down oblique beams to spare spinal cord and normal structures. However, there is no optimum technique to determine oblique beam angles when a CT simulation is not available. Impact of oblique beam angle was investigated in this study. Fifteen patients with centrall...
journal_title:International journal of cancer
pub_type: 杂志文章
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更新日期:2000-12-20 00:00:00
abstract::Mouse IFN gamma preparations purified 30-fold were found to have direct cytolytic activity against a number of tumor and normal cells. Cell killing was determined using a sensitive, rapid and accurate assay which employed very low numbers of cells and very small quantities of interferon. The cytolytic activity of IFN ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910300111
更新日期:1982-07-15 00:00:00
abstract::The impact of a human papillomavirus (HPV) vaccine on development of cervical intraepithelial neoplasia grade 2-3 or adenocarcinoma in situ (CIN2-3/AIS) in women with ongoing HPV16 or 18 infections prevaccination is reported. Seventeen thousand six-hundred and twenty-two women aged 16-26 were enrolled in 1 of 2 random...
journal_title:International journal of cancer
pub_type: 杂志文章,随机对照试验
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更新日期:2011-12-01 00:00:00
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journal_title:International journal of cancer
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更新日期:1997-05-29 00:00:00
abstract::Like the majority of tumor cells, ovarian cancer cell growth is critically dependent on their neovascularization. Adhesion molecules and cellular events that lead to ovarian tumor cell interactions with endothelial extracellular matrix surrounding the vasculature are poorly identified. To understand the role of alphav...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.10433
更新日期:2002-06-20 00:00:00
abstract::The activity of systemic and in situ natural killer (NK) cells was measured in 3- to 5-week-old CBA mice with progressively growing murine sarcoma virus (MSV)-induced tumors. Splenic NK activity was depressed in tumor-bearing mice. NK activity was quite low or not detectable in unfractionated cell suspensions from the...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910270218
更新日期:1981-02-15 00:00:00
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journal_title:International journal of cancer
pub_type: 杂志文章
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更新日期:2001-11-01 00:00:00
abstract::Protein inhibitor of activated signal transducer and activator of transcription 3 (STAT3) (PIAS3) is an endogenous inhibitor of STAT3 that negatively regulates STAT3 transcriptional activity and cell growth and demonstrates limited expression in the majority of human squamous cell carcinomas of the lung. In this study...
journal_title:International journal of cancer
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更新日期:2014-03-01 00:00:00
abstract::The influence of prolonged treatment with antilymphocyte globulin on tumour incidence in BN/a and BN/b mice was studied. One ALG sample appeared to be highly leukaemogenic in two independent experiments. All treated mice developed, after a short latency period, non-thymic lymphomas with involvement of abdominal lymph ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910180615
更新日期:1976-12-15 00:00:00
abstract::Single-cell suspensions prepared from five human melanomas, grown serially as xenografts in athymic nude mice, were exposed in vitro to increasing concentrations of DTIC (Dacarbazine), CCNU (Lomustine), procarbazine, vinblastine, and the cancerostatic lectins abrin and ricin. The in vitro chemosensitivity of the cells...
journal_title:International journal of cancer
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doi:10.1002/ijc.2910260604
更新日期:1980-12-15 00:00:00
abstract::The miR-34 family members are direct transcriptional targets of tumor suppressor p53, and loss of miR-34 function can impair p53-mediated cell cycle arrest and apoptosis. A potentially functional SNP rs4938723 (T > C) was found in the promoter region of pri-miR-34b/c (423 bp from the transcription start site), located...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.25342
更新日期:2011-01-15 00:00:00
abstract::Vascular endothelial growth factor-A (VEGF-A) plays an important role in tumour angiogenesis and cancer progression. VEGF gene variation may influence VEGF levels and therefore cancer susceptibility and progression. We studied the role of VEGF single nucleotide polymorphisms and haplotypes in breast cancer susceptibil...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.22772
更新日期:2007-09-01 00:00:00
abstract::Chemotherapy is a well-established risk factor for acute myeloid leukemia (AML) but little is known about other prescription drugs and AML risk. We report data from a population-based Los Angeles County study in which 299 matched case-control pairs had complete data on prescription drug use and 88% of cases were subty...
journal_title:International journal of cancer
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更新日期:2005-04-20 00:00:00
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journal_title:International journal of cancer
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journal_title:International journal of cancer
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journal_title:International journal of cancer
pub_type: 临床试验,杂志文章,多中心研究
doi:
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journal_title:International journal of cancer
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更新日期:2000-02-15 00:00:00
abstract::Increasing evidences indicate that CXCR4/CXCL12 signaling pathway plays a pivotal role in the process of distant site metastasis that accounts for more than 90% of prostate cancer related deaths in patients. Thus, novel drugs that can downregulate CXCR4/CXCL12 axis have a great potential in the treatment of metastatic...
journal_title:International journal of cancer
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doi:10.1002/ijc.26120
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journal_title:International journal of cancer
pub_type: 杂志文章
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更新日期:2001-01-01 00:00:00
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journal_title:International journal of cancer
pub_type: 杂志文章
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更新日期:2010-04-01 00:00:00
abstract::We investigated whether the concentration of fibronectin (FN) in the cerebrospinal fluid (CSF) could be used for identifying patients with subclinical blast-cell infiltration in the central nervous system (CNS) and an increased risk of CNS relapse later in the course of their leukemia. Our series comprised 36 children...
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journal_title:International journal of cancer
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journal_title:International journal of cancer
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更新日期:2005-05-10 00:00:00
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journal_title:International journal of cancer
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更新日期:2002-04-10 00:00:00