Lapatinib in combination with paclitaxel plays synergistic antitumor effects on esophageal squamous cancer.

Abstract:

PURPOSE:Paclitaxel-based chemoradiotherapy was proven to be efficacious in treating patients with advanced esophageal cancer. However, the toxicity and the development of resistance limited its anticancer efficiency. The present study was to evaluate the antitumor effects of lapatinib, a dual tyrosine inhibitor of both epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2), combined with paclitaxel on the esophageal squamous cancer. METHODS:MTT assays were used to evaluate the effects of the combination of lapatinib and paclitaxel on the growth of esophageal squamous cancer cell lines (KYSE150, KYSE450, KYSE510 and TE-7). The activity of the combination of two agents on cell invasion, migration and apoptosis was measured by wound healing assay, transwell assay and Annexin V-FITC/PI stain assay. Western blot assay was used to analyze the effects of the two agents on the EGFR/HER2 signaling. The in vivo efficacy was evaluated in KYSE450 xenograft nude mouse model. RESULTS:The combination of lapatinib and paclitaxel was highly synergistic in inhibiting cell growth with a combination index of < 1, and suppressed significantly the invasion and migration capability of esophageal squamous cancer cells. Esophageal squamous cancer cells displayed increased rates of apoptosis after treatment with lapatinib plus paclitaxel. The phosphorylated EGFR and HER2 as well as the activation of downstream molecules MAPKs and AKT significantly decreased when exposed to lapatinib and paclitaxel. In vivo studies showed that the combination of two agents had greater antitumor efficacy than either agent alone. CONCLUSIONS:The combination of lapatinib with paclitaxel showed synergistic antitumor activity, suggesting their potential in treating patients with esophageal squamous cancer.

authors

Guo XF,Li SS,Zhu XF,Dou QH,Liu D

doi

10.1007/s00280-018-3627-3

subject

Has Abstract

pub_date

2018-09-01 00:00:00

pages

383-394

issue

3

eissn

0344-5704

issn

1432-0843

pii

10.1007/s00280-018-3627-3

journal_volume

82

pub_type

杂志文章
  • Synergistic antitumor activity of TRAIL combined with chemotherapeutic agents in A549 cell lines in vitro and in vivo.

    abstract:PURPOSE:To investigate the synergistic cytotoxicity of TRAIL in combination with chemotherapeutic agents in A549 cell lines, we systematically evaluated the cytotoxicity of TRAIL alone and TRAIL in combination with cisplatin, paclitaxel (Taxol) or actinomycin D in A549 cell lines in vitro and in vivo, and whether the s...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-004-0867-1

    authors: Fan QL,Zou WY,Song LH,Wei W

    更新日期:2005-02-01 00:00:00

  • A phase II study of pirarubicin in patients with advanced recurrent head and neck squamous cell carcinoma.

    abstract:BACKGROUND:Head and neck squamous carcinoma (HNSCC) is a chemotherapy-sensitive tumour, but this sensitivity is not reflected in an impact on survival. The study of new drugs is therefore indicated. Pirarubicin (4'-O-tetrahydropyranyl-doxorubicin) has a higher preclinical index than doxorubicin, with low cardiotoxicity...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1007/BF00686275

    authors: De Mulder PH,Cappelaere P,Cognetti F,Verweij J,Schornagel JH,Vermorken JB,Kirkpatrick A,Lefebvre JL

    更新日期:1994-01-01 00:00:00

  • A phase I trial of weekly paclitaxel, 13- cis-retinoic acid, and interferon alpha in patients with prostate cancer and other advanced malignancies.

    abstract:PURPOSE:Based on prior studies demonstrating the effect of 13- cis-retinoic acid and interferon alpha (CRA/IFN) in decreasing the expression of the antiapoptotic protein bcl-2, our prior clinical study of CRA/IFN with paclitaxel (TAX) administered every 3 weeks, and data demonstrating increased activity of weekly TAX a...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1007/s00280-003-0644-6

    authors: Thalasila A,Poplin E,Shih J,Dvorzhinski D,Capanna T,Doyle-Lindrud S,Beers S,Goodin S,Rubin E,DiPaola RS

    更新日期:2003-08-01 00:00:00

  • Cellular pharmacology of 1-beta-D-arabinofuranosylcytosine in human myeloid, B-lymphoid and T-lymphoid leukemic cells.

    abstract::The in vitro inhibitory action and metabolism of 1-beta-D-arabinofuranosylcytosine (ara-C) on human myeloid (HL-60), B-lymphoid (RPMI-8392), and T-lymphoid (Molt-3) leukemic cells was compared. Ara-C produced greater inhibitory effects in Molt-3 cells than in either HL-60 or RPMI-8392 cells. At a 48 h exposure, ara-C ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00689099

    authors: Momparler RL,Onetto-Pothier N,Bouffard DY,Momparler LF

    更新日期:1990-01-01 00:00:00

  • Activity of irofulven (6-hydroxymethylacylfulvene) in the treatment of glioblastoma multiforme-derived xenografts in athymic mice.

    abstract:PURPOSE:This study was conducted to define the activity of irofulven in the treatment of a series of xenografts derived from human glioblastoma multiforme growing subcutaneously and intracranially in athymic nude mice. METHODS:Athymic mice bearing subcutaneous or intracranial tumors were treated with irofulven at a 10...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s002800100358

    authors: Friedman HS,Keir ST,Houghton PJ,Lawless AA,Bigner DD,Waters SJ

    更新日期:2001-11-01 00:00:00

  • Clinical and in vitro studies of the correlation between MGMT and the effect of streptozocin in pancreatic NET.

    abstract:PURPOSE:This study aimed to determine the correlation between DNA repair enzyme O6-methylguanine DNA methyltransferase (MGMT) status and the response to streptozocin in advanced well-differentiated pancreatic neuroendocrine tumors (WD panNETs). METHODS:To test the hypothesis that MGMT deficiency was required for an al...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-018-3700-y

    authors: Hijioka S,Sakuma K,Aoki M,Mizuno N,Kuwahara T,Okuno N,Hara K,Yatabe Y

    更新日期:2019-01-01 00:00:00

  • Platinum drug effects on the expression of genes in the polyamine pathway: time-course and concentration-effect analysis based on Affymetrix gene expression profiling of A2780 ovarian carcinoma cells.

    abstract:PURPOSE:As a follow-up to our previous findings that platinum drugs induce a key enzyme in polyamine catabolism, gene expression profiling and mathematical modeling were used to define the effects of cisplatin and oxaliplatin on the expression of polyamine metabolic pathway genes in A2780 human ovarian carcinoma cells....

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-006-0325-3

    authors: Varma R,Hector S,Greco WR,Clark K,Hawthorn L,Porter C,Pendyala L

    更新日期:2007-05-01 00:00:00

  • Effect of body weight on the pharmacokinetics of cyclophosphamide in breast cancer patients.

    abstract::Cyclophosphamide pharmacokinetics have been studied in 16 female patients with advanced breast cancer. The group included 7 patients who were greater than 20%, less than or equal to 30% over ideal body weight and 5 patients who were greater than 30% over ideal body weight. Cyclophosphamide plasma elimination half-live...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1007/BF00570489

    authors: Powis G,Reece P,Ahmann DL,Ingle JN

    更新日期:1987-01-01 00:00:00

  • Mechanism-based modeling of the clinical effects of bevacizumab and everolimus on vestibular schwannomas of patients with neurofibromatosis type 2.

    abstract:PURPOSE:To describe the natural growth of vestibular schwannoma in patients with neurofibromatosis type 2 and to predict tumor volume evolution in patients treated with bevacizumab and everolimus. METHODS:Clinical data, including longitudinal tumor volumes in patients treated by bevacizumab (n = 13), everolimus (n = 7...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-016-3046-2

    authors: Ouerdani A,Goutagny S,Kalamarides M,Trocóniz IF,Ribba B

    更新日期:2016-06-01 00:00:00

  • The role of comparative pharmacokinetics in the planning of human dose escalation: the experience with diacetyldianhydrogalactitol.

    abstract::The pharmacokinetics of diacetyldianhydrogalactitol (DADAG) was compared in mice, rats, and humans. The ratios of human therapeutic dose (ThD) to the LD10 were 8 and 5 in mice and rats, respectively. The ratios of the corresponding AUCs of DADAG were 20 and 17, whereas those of dianhydrogalactitol (DAG), the main, act...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00257306

    authors: Kerpel-Fronius S,Erdélyi-Tóth V,Somfai-Relle S,Csetényi J,Kovács P,Ujj G,Kanyár B

    更新日期:1988-01-01 00:00:00

  • CDDO-Me, a synthetic triterpenoid, inhibits expression of IL-6 and Stat3 phosphorylation in multi-drug resistant ovarian cancer cells.

    abstract::Previous studies have identified interleukin 6 (IL-6) as an important cytokine with prognostic significance in ovarian cancer. Activation of the IL-6-Stat3 pathway contributes to tumor cell growth, survival and drug resistance in several cancers, including ovarian cancer. To explore potential therapeutic strategies fo...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-008-0785-8

    authors: Duan Z,Ames RY,Ryan M,Hornicek FJ,Mankin H,Seiden MV

    更新日期:2009-03-01 00:00:00

  • Pharmacokinetics of high-dose intravenous melphalan in children and adults with forced diuresis. Report in 26 cases.

    abstract::The pharmacokinetic parameters of the alkylating agent melphalan were determined in 15 children and 11 adults with advanced malignant solid tumors. High IV bolus doses of 140 mg/m2 were given under standard hyperhydration conditions and followed by autologous bone marrow grafting. In all cases the time-concentration c...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00293997

    authors: Ardiet C,Tranchand B,Biron P,Rebattu P,Philip T

    更新日期:1986-01-01 00:00:00

  • Primary breast tumor levels of suspected molecular determinants of cellular sensitivity to cyclophosphamide, ifosfamide, and certain other anticancer agents as predictors of paired metastatic tumor levels of these determinants. Rational individualization

    abstract:PURPOSE:Cyclophosphamide is one of the most frequently used agents in the neoadjuvant, adjuvant, and high-dose chemotherapeutic treatment of breast cancers. Preclinical models indicate that cellular sensitivity to cyclophosphamide and other oxazaphosphorines, e.g., ifosfamide, is inversely related to the cellular conte...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s002800000208

    authors: Sreerama L,Sládek NE

    更新日期:2001-03-01 00:00:00

  • Effect of cyclosporine coadministration on the pharmacokinetics of eltrombopag in healthy volunteers.

    abstract:PURPOSE:Eltrombopag is indicated in patients with severe aplastic anemia (SAA) refractory to prior immunosuppressive therapy. The combination of eltrombopag and immunosuppressive therapy (such as cyclosporine) is currently being evaluated in patients with treatment-naive SAA. Cyclosporine is a human breast cancer resis...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1007/s00280-018-3677-6

    authors: Aslanis V,Zhang J,Lomeli B,Grosch K,Ouatas T

    更新日期:2018-11-01 00:00:00

  • Adjuvant intra-arterial 5-fluoruracil, leucovorin, epirubicin and carboplatin with or without systemic gemcitabine after curative resection for pancreatic adenocarcinoma.

    abstract:BACKGROUND:The role of adjuvant therapy in pancreatic cancer remains controversial. Gemcitabine given systemically seems to be effective; intra-arterial chemotherapy (IAC) has a deep rationale. PATIENTS AND METHODS:The goal was to evaluate the impact of postoperative IAC followed or not by systemic gemcitabine in pati...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 临床试验,杂志文章,多中心研究

    doi:10.1007/s00280-006-0200-2

    authors: Cantore M,Serio G,Pederzoli P,Mambrini A,Iacono C,Pulica C,Capelli P,Lombardi M,Torri T,Pacetti P,Pagani M,Fiorentini G

    更新日期:2006-10-01 00:00:00

  • Pharmacokinetics of temozolomide given three times a day in pediatric and adult patients.

    abstract:PURPOSE:To characterize and compare pharmacokinetic parameters in children and adults treated with temozolomide (TMZ) administered for 5 days in three doses daily, and to evaluate the possible relationship between AUC values and hematologic toxicity. METHODS:TMZ pharmacokinetic parameters were characterized in pediatr...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 临床试验,杂志文章,多中心研究

    doi:10.1007/s00280-003-0677-x

    authors: Riccardi A,Mazzarella G,Cefalo G,Garrè ML,Massimino M,Barone C,Sandri A,Ridola V,Ruggiero A,Mastrangelo S,Lazzareschi I,Caldarelli M,Maira G,Madon E,Riccardi R

    更新日期:2003-12-01 00:00:00

  • Flavone acetic acid and plasma protein binding.

    abstract::Both the capacity of healthy human, cancer patient, and mouse plasma proteins to bind flavone acetic acid (FAA) and the qualitative differences in the plasma protein-binding site were studied. The binding capacity of plasma proteins for FAA was saturated within the therapeutic range in both species. The binding of FAA...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00689272

    authors: Brodfuehrer J,Valeriote F,Chan K,Heilbrun L,Corbett T

    更新日期:1990-01-01 00:00:00

  • A phase I study of MN-029 (denibulin), a novel vascular-disrupting agent, in patients with advanced solid tumors.

    abstract:PURPOSE:MN-029 (denibulin HCl) is a novel vascular-disrupting agent that reversibly inhibits microtubule assembly, resulting in disruption of the cytoskeleton of tumor vascular endothelial cells. This study determined the safety, pharmacokinetics, and acute anti-vascular effects of MN-029. METHODS:Patients were treate...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-011-1565-4

    authors: Ricart AD,Ashton EA,Cooney MM,Sarantopoulos J,Brell JM,Feldman MA,Ruby KE,Matsuda K,Munsey MS,Medina G,Zambito A,Tolcher AW,Remick SC

    更新日期:2011-10-01 00:00:00

  • The clinical pharmacology of the adenosine deaminase inhibitor 2'-deoxycoformycin.

    abstract::2'-deoxycoformycin (2'-dCF; Pentostatin), a stoichiometric inhibitor of mammalian adenosine deaminase (ado deaminase), exhibits immunosuppressive and antilymphocytic activity in animal test systems. A clinical pharmacology/phase I study of 2'-dCF administered as a single agent has been completed (18 patients). Dose le...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00435411

    authors: Smyth JF,Paine RM,Jackman AL,Harrap KR,Chassin MM,Adamson RH,Johns DG

    更新日期:1980-01-01 00:00:00

  • Effects of 5-fluorouracil on cytotoxicity and RNA metabolism in human colonic carcinoma cells.

    abstract::The cytotoxicity of 5-fluorouracil (5-FU) is due in part to the incorporation of the base into RNA molecules. We assessed the cytotoxicity of 5-FU in human colonic carcinoma HT-29 cells and examined mRNA activity (measured by protein biosynthesis in vivo and in vitro) and the maturation of rRNA precursors as two possi...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00694336

    authors: Greenhalgh DA,Parish JH

    更新日期:1989-01-01 00:00:00

  • Clinical and laboratory studies of the novel cyclin-dependent kinase inhibitor dinaciclib (SCH 727965) in acute leukemias.

    abstract:PURPOSE:Dinaciclib inhibits cyclin-dependent kinases 1, 2, 5, and 9 with a better therapeutic index than flavopiridol in preclinical studies. This study assessed the activity of dinaciclib in acute leukemia both in the clinic and in vitro. METHODS:Adults with relapsed/refractory acute myeloid leukemia (n = 14) and acu...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1007/s00280-013-2249-z

    authors: Gojo I,Sadowska M,Walker A,Feldman EJ,Iyer SP,Baer MR,Sausville EA,Lapidus RG,Zhang D,Zhu Y,Jou YM,Poon J,Small K,Bannerji R

    更新日期:2013-10-01 00:00:00

  • A pharmacological study of celecoxib and gemcitabine in patients with advanced pancreatic cancer.

    abstract:PURPOSE:To evaluate whether celecoxib alters the conversion of gemcitabine into its active metabolite, difluorodeoxycytidine triphosphate (dFdCTP), in peripheral blood mononuclear cells (PBMCs). METHODS:Patients with advanced pancreatic cancer who had not received chemotherapy and had acceptable organ function were el...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1007/s00280-004-0916-9

    authors: Xiong HQ,Plunkett W,Wolff R,Du M,Lenzi R,Abbruzzese JL

    更新日期:2005-06-01 00:00:00

  • Gef gene therapy enhances the therapeutic efficacy of doxorubicin to combat growth of MCF-7 breast cancer cells.

    abstract:PURPOSE:The potential use of combined therapy is under intensive study including the association between classical cytotoxic and genes encoding toxic proteins which enhanced the antitumour activity. The main aim of this work was to evaluate whether the gef gene, a suicide gene which has a demonstrated antiproliferative...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-009-1135-1

    authors: Prados J,Melguizo C,Rama AR,Ortiz R,Segura A,Boulaiz H,Vélez C,Caba O,Ramos JL,Aránega A

    更新日期:2010-05-01 00:00:00

  • V79 Chinese hamster lung cells resistant to the bis-alkylator bizelesin are multidrug-resistant.

    abstract::Bizelesin (U-77779) is a highly potent bis-alkylating antitumor agent that is effective against several tumor systems in vitro and in vivo. V79 cells that were 125- to 250-fold resistant to bizelesin developed after constant exposure to gradually increasing concentrations of the drug. Resistant cells exhibited a multi...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00686110

    authors: Butryn RK,Smith KS,Adams EG,Abraham I,Stackpole J,Sampson KE,Bhuyan BK

    更新日期:1994-01-01 00:00:00

  • Modulation of mitomycin C-induced multidrug resistance in vitro.

    abstract::A series of in vitro cytotoxicity studies were performed to achieve pharmacologic reversal of resistance to the alkylating agent mitomycin (MMC) in L-1210 leukemia cells. A multidrug-resistant (MDR), P-glycoprotein-positive cell line, RL-1210/.1 [11], was exposed to potential MDR modulators in the absence or presence ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00685114

    authors: Dorr RT,Liddil JD

    更新日期:1991-01-01 00:00:00

  • Determination of pharmacokinetic values of calicheamicin-antibody conjugates in mice by plasmon resonance analysis of small (5 microl) blood samples.

    abstract:PURPOSE:The present study aims to establish a method that provides fast, precise and reproducible pharmacokinetic (PK) parameters of antibody-calicheamicin conjugates. The method should discriminate between PK of the antibody moiety and PK of the conjugated calicheamicin (CM). METHODS:The conjugates gemtuzumab ozogami...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-007-0560-2

    authors: Boghaert ER,Khandke KM,Sridharan L,Dougher M,DiJoseph JF,Kunz A,Hamann PR,Moran J,Chaudhary I,Damle NK

    更新日期:2008-05-01 00:00:00

  • All-trans retinoic acid significantly increases 5-year survival in patients with acute promyelocytic leukemia: long-term follow-up of the New York study.

    abstract::All-trans retinoic acid (ATRA) induces a high incidence of complete remission (CR) in patients with acute promyelocytic leukemia (APL); however, the magnitude of this agent's contribution to increased rates of cure of this disease has not yet been established. From 1990 to 1995 we used RA as remission induction therap...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s002800051057

    authors: Soignet S,Fleischauer A,Polyak T,Heller G,Warrell RP Jr

    更新日期:1997-01-01 00:00:00

  • Cellular glutathione as a protective agent against 4-hydroperoxycyclophosphamide cytotoxicity in K-562 cells.

    abstract::Exposure of cells of the K-562 erythroleukemia cell line to 4-hydroperoxycyclophosphamide (4-HC), an analog of activated cyclophosphamide, causes a concentration-dependent inhibition of in vitro colony formation by these cells. For investigation of the role of glutathione (GSH) in the metabolism of 4-HC, GSH levels of...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF02994088

    authors: Peters RH,Ballard K,Oatis JE,Jollow DJ,Stuart RK

    更新日期:1990-01-01 00:00:00

  • Positive relationship between subsequent chemotherapy and overall survival in pancreatic cancer: meta-analysis of postprogression survival for first-line chemotherapy.

    abstract:PURPOSE:To gain a better understanding of the impact of postprogression survival (PPS) and post-trial anticancer therapy on overall survival (OS) in first-line pancreatic cancer patients. METHODS:A literature search identified 54 randomized trials, focusing on gemcitabine monotherapy to eliminate effects of heterogene...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,meta分析,评审

    doi:10.1007/s00280-017-3263-3

    authors: Kasuga A,Hamamoto Y,Takeuchi A,Kawasaki K,Suzuki T,Hirata K,Sukawa Y,Takaishi H,Kanai T

    更新日期:2017-03-01 00:00:00

  • Ara-C affects formation of cancer cell DNA synthesome replication intermediates.

    abstract:PURPOSE:An intact and fully functional multiprotein DNA replication complex (DNA synthesome) from human as well as from murine mammary carcinoma cells was first isolated and characterized in our laboratory. The human cell synthesome supports the in vitro origin-specific simian virus 40 (SV40) DNA replication reaction i...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s002800050046

    authors: Abdel-Aziz W,Jiang HY,Hickey RJ,Malkas LH

    更新日期:2000-01-01 00:00:00