Evaluation of synergism by a novel three-dimensional model for the combined action of cisplatin and etoposide on the growth of a human small-cell lung-cancer cell line, SBC-3.


: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.


Int J Cancer


Kanzawa F,Nishio K,Fukuoka K,Fukuda M,Kunimoto T,Saijo N




Has Abstract


1997-05-02 00:00:00














  • Telomere homolog oligonucleotides induce apoptosis in malignant but not in normal lymphoid cells: mechanism and therapeutic potential.

    abstract::Human B- or T-cell lymphoma lines and primary murine lymphomas were treated with DNA oligonucleotides homologous to the telomere (TTAGGG repeat; "T-oligo"), either alone or in combination with standard, widely-used anticancer chemotherapeutic agents. T-oligo induces cell cycle arrest and apoptosis in cultured human or...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Longe HO,Romesser PB,Rankin AM,Faller DV,Eller MS,Gilchrest BA,Denis GV

    更新日期:2009-01-15 00:00:00

  • Biologic and antigenic characteristics of Epstein-Barr virus-related Herpesviruses of chimpanzees and baboons.

    abstract::Leukocyte-transforming agents were isolated in baboon leukocytes inoculated with oral excretions from immunosuppressed chimpanzees. The transformed lymphoblasts had B cell surface markers and harbored herpes-type virus particles; 5-10% of the cells contained cytoplasmic antigens reactive with Epstein-Barr virus (EBV)-...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Gerber P,Kalter SS,Schidlovsky G,Peterson WD Jr,Daniel MD

    更新日期:1977-09-15 00:00:00

  • Genetic polymorphisms in the one-carbon metabolism pathway and breast cancer risk: a population-based case-control study and meta-analyses.

    abstract::Epidemiological evidence suggests that intake of folate and other B-vitamins and genetic variants in the one-carbon metabolism pathway could influence the risk of breast cancer. Previous studies have focused on 2 polymorphisms in the methylenetetrahydrofolate gene (MTHFR A222V and E429A); however, findings are inconcl...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Lissowska J,Gaudet MM,Brinton LA,Chanock SJ,Peplonska B,Welch R,Zatonski W,Szeszenia-Dabrowska N,Park S,Sherman M,Garcia-Closas M

    更新日期:2007-06-15 00:00:00

  • CDKN2A region polymorphism and genetic susceptibility to melanoma in the melim swine model of familial melanoma.

    abstract::Some herds of miniature swine are genetically predisposed to cutaneous melanoma. To test if swine melanoma susceptibility could be linked to the CDKN2A gene, which is involved in a proportion of 9p21-linked human familial melanoma, we performed a genetic analysis of miniature pigs of the MeLiM strain. F(1) and backcro...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Le Chalony C,Renard C,Vincent-Naulleau S,Crechet F,Leplat JJ,Tricaud Y,Horak V,Gruand J,Le Roy P,Frelat G,Geffrotin C

    更新日期:2003-02-20 00:00:00

  • A cross-sectional investigation of breast density and insulin-like growth factor I.

    abstract::Our study investigated the association of breast cancer risk as assessed by mammographic density with insulin-like growth factor I (IGF-I) and one of its binding proteins (IGFBP-3) in healthy premenopausal women with different ethnic backgrounds. In a cross-sectional design, we analyzed the baseline mammograms and fas...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Maskarinec G,Williams AE,Kaaks R

    更新日期:2003-12-20 00:00:00

  • Acquisition of immunogenicity by AKR leukemic cells following DNA-mediated gene transfer is associated with the reduction of constitutive reactive superoxide radicals.

    abstract::We have employed the DNA-mediated gene transfer method to introduce the allogenic major-histocompatibility-complex(MHC)-class-I gene H-2Kb into the K36.16 tumor cells, H-2k, in order to generate tumor-specific immunity. The acquisition of immunogenicity by the H-2Kb-transformed clones following gene transfer is associ...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Chia KY,Lim SP,Oei AA,Sabapathy TK,Hui KM

    更新日期:1994-04-15 00:00:00

  • Breast cancer cells induce osteoclast formation by stimulating host IL-11 production and downregulating granulocyte/macrophage colony-stimulating factor.

    abstract::Breast cancer cells frequently metastasize to the skeleton, where they induce OCL formation and activity, resulting in extensive bone destruction. However, the mechanisms by which breast cancer cells mediate increased osteolysis remain unclear. To elucidate this point, we investigated how 3 human breast cancer cell li...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Morgan H,Tumber A,Hill PA

    更新日期:2004-05-01 00:00:00

  • A simple and effective method for cancer immunotherapy by inactivated allogeneic leukocytes infusion.

    abstract::Allogeneic mixed leukocytes reaction has been reported to activate vast numbers of T lymphocytes and produce large amounts of type 1 cytokines that are linked to an initiation of antitumor immunity. Using poor immunogeneic B16-F10 and Lewis lung carcinoma (LLC) tumor model, we evaluated the effects of inactivated allo...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Su X,Guo S,Zhou C,Wang D,Ma W,Zhang S

    更新日期:2009-03-01 00:00:00

  • Socioeconomic status and childhood acute lymphocytic leukemia incidence in São Paulo, Brazil.

    abstract::To investigate the association of childhood ALL and SES, we collected data on 507 children aged 0-14 years diagnosed with ALL between 1997 and 2002 from the population-based Cancer Registry of São Paulo, Brazil, covering 96 districts. Each child was assigned to an SES category based on the district of residence at dia...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Ribeiro KB,Buffler PA,Metayer C

    更新日期:2008-10-15 00:00:00

  • Chromosome stability in tonsillar squamous cell carcinoma is associated with HPV16 integration and indicates a favorable prognosis.

    abstract::Tonsillar squamous cell carcinoma (TSCC) is frequently associated with human papillomavirus (HPV) and chromosome instability. Data from cellular model systems are, however, controversial concerning a relation between HPV and chromosome instability development. Here we studied this association in 77 primary TSCC with k...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Mooren JJ,Kremer B,Claessen SM,Voogd AC,Bot FJ,Peter Klussmann J,Huebbers CU,Hopman AH,Ramaekers FC,Speel EJ

    更新日期:2013-04-15 00:00:00

  • Occupation and risk of cancer of the lower urinary tract among men. A case-control study.

    abstract::Data from a hospital-based matched case-control study with 531 male pairs were analyzed for risks of cancer of the lower urinary tract associated with previous employment and particular occupational exposures. Statistically significant odds ratios were obtained for ever-employment as mining workers (2.0), turners (2.3...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Claude JC,Frentzel-Beyme RR,Kunze E

    更新日期:1988-03-15 00:00:00

  • Uptake of prostate-specific antigen testing for early prostate cancer detection in Sweden.

    abstract::The aim of our study was to estimate uptake of prostate-specific antigen (PSA) testing in an entire country, including time trends and geographical differences. Data from the Swedish Cancer Register on prostate cancer incidence between 1980 and 2007 and published data from the Gothenburg branch of the European randomi...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Jonsson H,Holmström B,Duffy SW,Stattin P

    更新日期:2011-10-15 00:00:00

  • Immunohistologic expression of blood-group antigens in normal human gastrointestinal tract and colonic carcinoma.

    abstract::A panel of 7 mouse monoclonal antibodies and the lectin from Ulex europeus, detecting blood-group-related antigens of the ABH and Lewis systems, have been used to define the distribution of these antigenic structures within the human gastrointestinal tract, and to characterize their expression and modulation in colore...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Cordon-Cardo C,Lloyd KO,Sakamoto J,McGroarty ME,Old LJ,Melamed MR

    更新日期:1986-05-15 00:00:00

  • Effect of different platelet agonists on intracellular free Ca++ concentrations in human tumor cells: possible role in tumor growth.

    abstract::Modulation of cytoplasmic Ca++ concentration is a mechanism common to signal transduction pathways regulating many cellular phenomena, including the interactions of tumors with the hemostatic system. We have investigated the pro-aggregating and pro-coagulant activities of human tumor cell lines cultured in vitro and t...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Saporiti A,Brocchieri A,Porta C,Moroni M,Grignani G

    更新日期:1995-07-28 00:00:00

  • Biological response of multicellular EMT6 spheroids to exogenous lactate.

    abstract::The influence of elevated lactate concentrations, as found in tumor microregions, on cellular growth, viability, and metabolic state was studied employing the multicellular spheroid model. Spheroids of EMT6/Ro cells were cultured at 37 degrees C in 5% or 20% (v/v) oxygen, using stirred media with various concentration...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Bourrat-Floeck B,Groebe K,Mueller-Klieser W

    更新日期:1991-03-12 00:00:00

  • Efficacy of intra-hepatectomy 5-FU on recurrence and metastasis of human hepatocellular carcinoma in nude mice.

    abstract::A novel intra-operative chemotherapy nude mouse model for human hepatocellular carcinoma (HCC) has been developed. Intra-peritoneal (i.p.) administration of 5-fluorouracil (5-FU) was begun 2 hr before hepatic resection of HCC and then continued post-operatively for 4 consecutive days. This regime, termed intra-hepatec...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Rashidi B,An Z,Sun FX,Li X,Tang ZY,Moossa AR,Hoffman RM

    更新日期:2001-01-15 00:00:00

  • Differential effects of retinoic acid on the in vitro growth and cell-surface glycoconjugates of 2 human head and neck squamous-cell carcinomas.

    abstract::As a part of an assessment of the potential use of retinoids in preventive and adjuvant treatment of HNSCC, we examined the effects of beta-all-trans retinoic acid (RA) on the growth and cell-surface glycoconjugates of 2 HNSCC cell lines. These lines, designated 1483 and 183A, were established from an untreated patien...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Lotan R,Sacks PG,Lotan D,Hong WK

    更新日期:1987-08-15 00:00:00

  • Impact of technology on cytology outcome in cervical cancer screening of young and older women.

    abstract::Little is known about age-dependent variation in outcomes of cervical cytology with modern technologies. This population-based study evaluated age-dependent changes after routine implementation of ThinPrep and SurePath technology in two independent laboratories, and controlled for time trends in a third laboratory usi...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Rask J,Lynge E,Franzmann M,Hansen B,Hjortebjerg A,Rygaard C,Schledermann D,Wåhlin A,Rebolj M

    更新日期:2014-05-01 00:00:00

  • Upregulation of galectins-1 and -3 in human colon cancer and their role in regulating cell migration.

    abstract::To probe the potential contribution of beta-galactoside-contributing epitopes and receptor proteins (gal-1 and gal-3) to colon malignancy, we first examined the expression of galectins and binding sites in clinical specimens by lectin and immunohistochemistry. Sixty-seven colonic surgical resections were studied, incl...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Hittelet A,Legendre H,Nagy N,Bronckart Y,Pector JC,Salmon I,Yeaton P,Gabius HJ,Kiss R,Camby I

    更新日期:2003-01-20 00:00:00

  • Mutant allele-specific imbalance modulates prognostic impact of KRAS mutations in colorectal adenocarcinoma and is associated with worse overall survival.

    abstract::The prognostic impact of distinct KRAS mutations in colorectal carcinomas is not fully characterized. We hypothesized that the prognostic impact of KRAS mutations is modulated by KRAS mutant allele-specific imbalance (MASI). KRAS MASI was assessed by sequencing electropherograms in KRAS-mutated colorectal carcinomas (...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Hartman DJ,Davison JM,Foxwell TJ,Nikiforova MN,Chiosea SI

    更新日期:2012-10-15 00:00:00

  • Estimating the impact of an organised screening programme on cervical cancer incidence: A 26-year study from northern Italy.

    abstract::The impact of the organised cervical cancer (CC) screening programmes implemented in Europe since the 1990s has been insufficiently evaluated. We investigated the changes in CC incidence following the introduction of a screening programme in the Emilia-Romagna Region (northern Italy). The study period was 1988-2013. T...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Bucchi L,Baldacchini F,Mancini S,Ravaioli A,Giuliani O,Vattiato R,Falcini F,Giorgi Rossi P,Campari C,Canuti D,Di Felice E,Sassoli de Bianchi P,Ferretti S,Bertozzi N,Biggeri A,Emilia-Romagna Region Workgroup for Cervical Scr

    更新日期:2019-03-01 00:00:00

  • Differences in lung cancer risk from smoking among Japanese, Chinese and Hawaiian women in Hawaii.

    abstract::The age-adjusted lung cancer incidence rates among Japanese, Chinese and Hawaiian women in Hawaii do not correlate to their respective cigarette smoking exposures. We conducted a case-control study to determine the lung cancer risk associated with smoking among these three ethnic groups of women by reviewing the medic...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Hinds MW,Stemmermann GN,Yang HY,Kolonel LN,Lee J,Wegner E

    更新日期:1981-03-15 00:00:00

  • Mutation analysis of the N-ras proto-oncogene in active and remission phase of human acute leukemias.

    abstract::DNA isolated from blood or bone-marrow samples from 18 patients with acute non-lymphocytic leukemia (ANLL) and 14 patients with acute lymphocytic leukemia (ALL) was analyzed for the presence of mutations in the N-ras gene. Using synthetic oligonucleotide probes we detected mutations in 5 cases of ANLL; 4 GGT----GAT tr...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Senn HP,Trân-Thang C,Wodnar-Filipowicz A,Jiricny J,Fopp M,Gratwohl A,Signer E,Weber W,Moroni C

    更新日期:1988-01-15 00:00:00

  • Efficacy of dendrimer-mediated angiostatin and TIMP-2 gene delivery on inhibition of tumor growth and angiogenesis: in vitro and in vivo studies.

    abstract::Gene transfer is an attractive approach to fight cancer by targeting cancer cells or their vasculature. Our study reports the inhibition of tumor growth and angiogenesis by a nonviral method using dendrimers associated with 36-mer anionic oligomers (ON36) for delivering angiostatin (Kringle 1-3) and tissue inhibitor o...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Vincent L,Varet J,Pille JY,Bompais H,Opolon P,Maksimenko A,Malvy C,Mirshahi M,Lu H,Vannier JP,Soria C,Li H

    更新日期:2003-06-20 00:00:00

  • Marine omega-3 fatty acid intake and survival of stage III colon cancer according to tumor molecular markers in NCCTG Phase III trial N0147 (Alliance).

    abstract::Marine omega-3 polyunsaturated fatty acids (MO3PUFAs) have anticancer properties and may improve colon cancer survival. However, it remains unknown whether the benefit differs by tumor molecular subtype. We examined data from a phase III randomized trial of FOLFOX or FOLFOX + cetuximab among 1,735 stage III colon canc...

    journal_title:International journal of cancer

    pub_type: 杂志文章,多中心研究,随机对照试验


    authors: Song M,Ou FS,Zemla TJ,Hull MA,Shi Q,Limburg PJ,Alberts SR,Sinicrope FA,Giovannucci EL,Van Blarigan EL,Meyerhardt JA,Chan AT

    更新日期:2019-07-15 00:00:00

  • Curcumin induces cell-arrest and apoptosis in association with the inhibition of constitutively active NF-kappaB and STAT3 pathways in Hodgkin's lymphoma cells.

    abstract::Although treatment of Hodgkin's lymphoma (HL) with a multi-drug approach has been very successful, its toxicity becomes evident after several years as secondary malignancies and cardiovascular disease. Therefore, the current goal in HL treatment is to find new therapies that specifically target the deregulated signali...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Mackenzie GG,Queisser N,Wolfson ML,Fraga CG,Adamo AM,Oteiza PI

    更新日期:2008-07-01 00:00:00

  • Multisite analysis of high-grade serous epithelial ovarian cancers identifies genomic regions of focal and recurrent copy number alteration in 3q26.2 and 8q24.3.

    abstract::High-grade serous epithelial ovarian cancer (HGS-EOC) is a systemic disease, with marked intra and interpatient tumor heterogeneity. The issue of spatial and temporal heterogeneity has long been overlooked, hampering the possibility to identify those genomic alterations that persist, before and after therapy, in the g...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Ballabio S,Craparotta I,Paracchini L,Mannarino L,Corso S,Pezzotta MG,Vescio M,Fruscio R,Romualdi C,Dainese E,Ceppi L,Calura E,Pileggi S,Siravegna G,Pattini L,Martini P,Delle Marchette M,Mangioni C,Ardizzoia A,Pelleg

    更新日期:2019-11-15 00:00:00

  • Screening of human brain tumors for SV40-related T antigen.

    abstract::A series of 39 human brain tumors has been screened for the presence or absence of SV40-related T antigen by the direct and indirect immunoperoxidase methods. Two tumors of ependymal origin (malignant ependymoma, choroid plexus papilloma) revealed markedly positive nuclear staining for T antigen both in vivo and in vi...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Tabuchi K,Kirsch WM,Low M,Gaskin D,Van Buskirk J,Maa S

    更新日期:1978-01-15 00:00:00

  • No excess risk of follicular lymphoma in kidney transplant and HIV-related immunodeficiency.

    abstract::Subtype-specific incidence patterns in populations at high risk of lymphoma offer insight into lymphomagenesis. The incidence profiles for the 2 most common non-Hodgkin lymphoma subtypes were compared for 2 immunodeficient populations, adults receiving a kidney transplant 1982-2003 (n = 7,730) or diagnosed with human ...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Vajdic CM,van Leeuwen MT,Turner JJ,McDonald AM,Webster AC,McDonald SP,Chapman JR,Kaldor JM,Grulich AE

    更新日期:2010-12-01 00:00:00

  • Developing new targeting strategy for androgen receptor variants in castration resistant prostate cancer.

    abstract::The presence of androgen receptor variant 7 (AR-V7) variants becomes a significant hallmark of castration-resistant prostate cancer (CRPC) relapsed from hormonal therapy and is associated with poor survival of CRPC patients because of lacking a ligand-binding domain. Currently, it still lacks an effective agent to tar...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Wang B,Lo UG,Wu K,Kapur P,Liu X,Huang J,Chen W,Hernandez E,Santoyo J,Ma SH,Pong RC,He D,Cheng YQ,Hsieh JT

    更新日期:2017-11-15 00:00:00