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::We have investigated the effect of pre-treatment with the anti-cancer drugs cisplatin and etoposide on the susceptibility of P815 murine mastocytoma cells to lysis by murine spleen-derived anti-CD3-activated killer-T (AK-T) cells. A 20 hr pre-treatment with cisplatin (0.2-2 microg/ml) or etoposide (0.01-1 microg/ml) r...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19971104)73:3<416::aid-ijc
更新日期:1997-11-04 00:00:00
abstract::Seminomas and control tissues were analyzed for several tumor markers. Very high levels of placental alkaline phosphatase (PLAP)-like enzyme levels were found in all 18 seminomas studied. The majority of the seminomas were of phenotype I, thus differing from palcental PLAP. The mean amount of enzyme protein as measure...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910400507
更新日期:1987-11-15 00:00:00
abstract::Anti-idiotypic antibodies that mimic tumour-associated antigens can stimulate anti-tumour T-cell responses. In this article, we have studied the role of Fc in the presentation of T-cell epitopes by 2 anti-idiotypic antibodies, 105AD7 and 708. The human monoclonal antibody 105AD7, which mimics CD55, stimulated strong i...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.1194
更新日期:2001-05-01 00:00:00
abstract::Galunisertib (LY2157299), a promising small-molecule inhibitor of the transforming growth factor-beta (TGF-β) receptor, is currently in mono- and combination therapy trials for various cancers including glioblastoma, hepatocellular carcinoma and breast cancer. Using genetically modified mouse models, we investigated t...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.32568
更新日期:2020-03-15 00:00:00
abstract::Since advanced melanoma remains practically incurable, early detection is an important step toward a reduction in mortality. High expectations are entertained for a technique known as dermoscopy or epiluminescence light microscopy; however, evaluation of pigmented skin lesions by this method is often extremely complex...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.10620
更新日期:2002-10-20 00:00:00
abstract::Kaposi's sarcoma is currently the most common tumor in Zimbabwe. The purpose of our study is to compare the effectiveness of supportive care vs. 3 intervention approaches, namely oral Etoposide, a 3-drug combination, and radiotherapy using quality of life (QOL) as the primary measure of success. In addition, our study...
journal_title:International journal of cancer
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1002/ijc.20606
更新日期:2005-02-10 00:00:00
abstract::A human ovarian adenocarcinoma cell line (PE04) has been established as a xenograft in nude mice. In vitro, this cell line is estrogen receptor (ER)-positive and its growth is stimulated by 17 beta-estradiol at concentrations between 10(-12) and 10(-6) M. When xenografted, PE04 cells remain ER-positive and also posses...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910550323
更新日期:1993-09-30 00:00:00
abstract::Leukemia stem cells (LSCs) might originate from malignant transformation of normal hematopoietic stem cells (HSCs), or alternatively, of progenitors in which the acquired mutations have re-installed a dysregulated self-renewal program. LSCs are on top of a hierarchy and generate leukemia cells with more differentiated...
journal_title:International journal of cancer
pub_type: 杂志文章,评审
doi:10.1002/ijc.26318
更新日期:2011-11-15 00:00:00
abstract::Cytokines play a crucial role in tumor initiation and progression. Here, we demonstrate that interleukin (IL)-6 is a key factor by driving tumor progression from benign to malignant, invasive tumors in the HaCaT-model of human skin carcinoma. IL-6 activates STAT3 and directly stimulates proliferation and migration of ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.25621
更新日期:2011-06-15 00:00:00
abstract::Serum and tumor tissue from breast cancer patients were evaluated for the presence of alpha subunit of hCG, by means of the specific radioimmunoassay. Elevated serum levels occurred in 0/50 (0%) of normal female controls, 1/17 (6%) of patients with benign breast disease, 3/53 (6%) of patients with primary breast cance...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910250508
更新日期:1980-05-15 00:00:00
abstract::In ovarian carcinomas, recurrence and acquired chemoresistance are the first leading causes of therapeutic failure and are responsible for the poor overall survival rate. Cisplatin exposure of sensitive cells has been previously associated with a down-regulation of Bcl-X(L) expression and apoptosis, whereas recurrence...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.24787
更新日期:2010-02-15 00:00:00
abstract::Kidney cancer often diagnosed at late stages when treatment options are severely limited. Thus, greater understanding of tumor metabolism leading ultimately to novel approaches to diagnosis is needed. Our laboratory has been utilizing metabolomics to evaluate compounds appearing in kidney cancer patients' biofluids at...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.26274
更新日期:2012-06-15 00:00:00
abstract::Dietary information from a case-control study of pancreatic cancer conducted in Metropolitan Toronto between 1983 and 1986 is reported. A total of 249 cases and 505 population-based controls completed quantitative diet histories from which total caloric intake and the intake of a number of nutrients were estimated. A ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910450405
更新日期:1990-04-15 00:00:00
abstract::Ovarian cancer risk is known to be reduced amongst women who have had children, but reported associations with breastfeeding are varied. Few studies have had sufficient power to explore reliably these associations by tumour histotype. In a prospective study of 1.1 million UK women, 8719 developed ovarian cancer during...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.31063
更新日期:2018-01-15 00:00:00
abstract::Two factors potentially determining the consistent overexpression of sialyl-Le(x) antigen in colon carcinoma and metastases were investigated: (i) the expression of the mucins MUC1 and MUC2, known to carry sialyl-Le(x), by Northern blotting; (ii) the extent of sialic acid O-acetylation, by Western blotting and HPLC. R...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19970717)72:2<258::aid-ijc
更新日期:1997-07-17 00:00:00
abstract::Environmental carcinogens often induce specific mutations in the p53 gene, apparent in tumors. The relation between aflatoxin B1 (AFB1 )-related hepatocellular carcinomas (HCCs) and hot spot at codon 249 of the p53 gene has received a great deal of attention, but its significance is still controversial. To clarify thi...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19990719)82:2<187::aid-ijc
更新日期:1999-07-19 00:00:00
abstract::Burkitt's lymphoma cells that vary in their phenotypic characteristics show significantly different degrees of susceptibility to radiation-induced apoptosis. Propensity to undergo apoptosis is reflected in the degradation of substrates such as DNA-dependent protein kinase but the status of bcl-2, c-myc and p53 has bee...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19980831)77:5<755::aid-ijc
更新日期:1998-08-31 00:00:00
abstract::The study of the relationship between dietary intake of fatty acids and the risk of breast cancer has not yielded definite conclusions with respect to causality, possibly because of methodological issues inherent to nutritional epidemiology. To evaluate the hypothesis of possible protection of n-3 polyunsaturated fatt...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19991126)83:5<585::aid-ijc
更新日期:1999-11-26 00:00:00
abstract::The mRNA levels of the ras-related human rhoA, rhoB and rhoC genes were studied in human breast-cancer cell lines (HBCal), and in normal and immortalized mammary epithelial cells (HMEC) by Northern blot analysis and in situ hybridization. In contrast to the ubiquitous rhoA and rhoC gene expression, dramatic variations...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910590320
更新日期:1994-11-01 00:00:00
abstract::Human papillomavirus (HPV) is now recognised as a major aetiological agent in the pathogenesis of oropharyngeal carcinoma (OPC). HPV-positive tumours are associated with better outcomes compared to HPV-negative tumours, possibly due to differences in their aetiology and/or the tumour microenvironment. Increased number...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.31852
更新日期:2019-01-15 00:00:00
abstract::Risks of 2nd primary cancer were assessed in all patients with cutaneous melanoma (12,460) and all patients with ocular melanoma (2,018) incident in Denmark from 1943 to 1989 and followed for totals of 88,667 person-years and 16,045 person-years, respectively. After cutaneous melanoma, 972 2nd cancers occurred. The ri...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910610606
更新日期:1995-06-09 00:00:00
abstract::Classical Hodgkin lymphoma (HL) is characterized by the presence of Hodgkin and Reed-Sternberg cells (H&RS) and a prominent lymphocytic infiltration. We previously reported Hodgkin-like adult T-cell leukemia/lymphoma (HL-like ATLL) (new WHO classification). Various CXC and CC chemokines are expressed on H&RS cells and...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.11301
更新日期:2003-09-20 00:00:00
abstract::A new permanent cell line (GRU-1) derived from the lymph-node metastasis of a human epithelioid sarcoma was established in tissue culture. Immunohistochemically, the original tumor had exhibited an intriguing potential for multidirectional differentiation with features of mesenchymal, epithelial and neural differentia...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910450126
更新日期:1990-01-15 00:00:00
abstract::The modulation of DNA topology by topoisomerase II plays a crucial role during chromosome condensation and segregation in mitosis and has thus become a highly attractive target for chemotherapeutic drugs. However, these drugs are highly toxic, and so new approaches are required. One such strategy is to target topoisom...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.21717
更新日期:2006-06-01 00:00:00
abstract::HPP1 is a recently discovered gene that is epigenetically silenced in a number of tumor types, suggesting a potential role as a tumor suppressor. However, whether HPP1 has tumor suppressor activity is not clearly known. We have sought to investigate the effects of HPP1 on tumor growth and survival and to identify sign...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.23202
更新日期:2008-04-01 00:00:00
abstract::The metastatic dissemination of cancer cells to remote areas of the body is the most problematic aspect in cancer patients. Among cancers, melanomas are notoriously difficult to treat due to their significantly high metastatic potential even during early stages. Hence, the establishment of advanced therapeutic approac...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.31982
更新日期:2019-07-15 00:00:00
abstract::We studied plasmin receptors on 3 MCF-7 sublines: MCF7, MCF7R which was derived by transfection with v-Ha-ras oncogene, and MCF7MF which has been studied for the secretion of procathepsin D in the presence of estrogen. All 3 sublines bound plasmin (Pli) with a much higher affinity than plasminogen (Pg). The number of ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910460432
更新日期:1990-10-15 00:00:00
abstract::RAGE is a central driver of tumorigenesis by sustaining an inflammatory tumor microenvironment. This study links the soluble forms of RAGE (sRAGE and esRAGE) with clinical outcome of melanoma patients. Moreover, tissue expression of RAGE was analyzed using immunohistochemistry on two independent tissue microarrays (TM...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.29619
更新日期:2015-12-01 00:00:00
abstract::Using high-throughput analyses and the TRANSFAC database, we characterized TF signatures of head and neck squamous cell carcinoma (HNSCC) subgroups by inferential analysis of target gene expression, correcting for the effects of DNA methylation and copy number. Using this discovery pipeline, we determined that human p...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.29558
更新日期:2015-10-15 00:00:00
abstract::Human kallikrein 11 (hK11/trypsin-like serine protease/TLSP, encoded by the KLK11 gene) is a member of the kallikrein family of secreted serine proteases. Recently, we developed a highly sensitive and specific immunoassay for hK11 and found that this protease is expressed in the prostate, stomach and trachea as well a...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.11296
更新日期:2003-09-10 00:00:00