A bivalent single-chain antibody-toxin specific for ErbB-2 and the EGF receptor.


:ErbB-2 and EGF receptors are often co-expressed in human tumors and have been shown to synergize in the transformation of cells in experimental model systems. Transactivation of ErbB-2 can occur via ligand-induced heterodimerization with EGF receptor or other members of the ErbB family of receptor tyrosine kinases. We have previously described the potent anti-tumoral activity of the monospecific single-chain antibody-toxins scFv(FRP5)-ETA and scFv(225)-ETA binding to, respectively, ErbB-2 and the EGF receptor. Here we report the construction and functional characterization of a novel bivalent, bispecific single-chain antibody-toxin, scFv2(FRP5/225)-ETA. The fusion protein consists of 2 scFv domains specific for ErbB-2 and the EGF receptor linked to a modified Pseudomonas exotoxin A. ScFv2(FRP5/225)-ETA displayed in vitro cell killing activity on tumor cells overexpressing either ErbB-2 or the EGF receptor similar to that of the monospecific toxins. It was more potent in vitro and in vivo in inhibiting the growth of tumor cells expressing both receptors. Treatment of A431 cells with scFv2(FRP5/225)-ETA led to an increase in EGF receptor and ErbB-2 phosphotyrosine content, most likely via the induction of receptor heterodimers. This may explain the enhanced toxicity of the bispecific antibody-toxin.


Int J Cancer


Schmidt M,Hynes NE,Groner B,Wels W




Has Abstract


1996-02-08 00:00:00














  • Breast cancer risk in relation to abortion: Results from the EPIC study.

    abstract::The role of spontaneous and induced abortion on breast cancer risk is examined among 267,361 women recruited into the European Prospective Investigation into Cancer and nutrition between 1992 and 2000. The data were collected from 20 centers, across 9 countries, and included information on a total of 4,805 women with ...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Reeves GK,Kan SW,Key T,Tjønneland A,Olsen A,Overvad K,Peeters PH,Clavel-Chapelon F,Paoletti X,Berrino F,Krogh V,Palli D,Tumino R,Panico S,Vineis P,Gonzalez CA,Ardanaz E,Martinez C,Amiano P,Quiros JR,Tormo MR,Kha

    更新日期:2006-10-01 00:00:00

  • Correlation of numerical and structural status of chromosome 16 with histological type and grade of non-invasive and invasive breast carcinomas.

    abstract::Loss of heterozygosity on chromosome arm 16q frequently occurs in human breast carcinomas regardless of the histological grade or type. To reveal whether the status of chromosome 16 corresponds to the histology of breast carcinomas, we examined the signal number of 16cen, 16q breakpoints and 1;16 fusions in the interp...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Tsuda H,Takarabe T,Hirohashi S

    更新日期:1999-08-20 00:00:00

  • Metastatic potential of murine fibrosarcoma cells is influenced by cell surface laminin.

    abstract::In order to examine the role of cell surface laminin in tumor metastasis we have utilized four well-characterized murine fibrosarcoma cell lines. Two of these lines were highly metastatic when injected into syngeneic mice while the remaining two lines were significantly less metastatic. Using indirect immunofluorescen...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Malinoff HL,McCoy JP Jr,Varani J,Wicha MS

    更新日期:1984-05-15 00:00:00

  • The presence of concanavalin-A(Con-A)-like molecules on natural-killer (NK)-sensitive target cells: their possible role in swainsonine-augmented human NK cytotoxicity.

    abstract::In the present study we examined the expression of concanavalin-A(Con-A)-like molecules on natural-killer (NK)-sensitive target cells and investigated their possible role in the human NK-cell phenomenon. The incubation of either peripheral-blood lymphocytes (PBL) or large granular lymphocytes (LGL) with swainsonine (S...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Yagita M,Noda I,Maehara M,Fujieda S,Inoue Y,Hoshino T,Saksela E

    更新日期:1992-10-21 00:00:00

  • Dietary catechins and epithelial cancer incidence: the Zutphen elderly study.

    abstract::The flavonoids, a group of more than 4,000 polyphenolic antioxidants, are potential cancer preventive components of fruits and vegetables. Catechins, one of the 6 major groups of flavonoids, are present in high concentrations in tea as well. Our objective was to evaluate the association between intake of catechins and...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Arts IC,Hollman PC,Bueno De Mesquita HB,Feskens EJ,Kromhout D

    更新日期:2001-04-15 00:00:00

  • miR-135b- and miR-146b-dependent silencing of calcium-sensing receptor expression in colorectal tumors.

    abstract::Studies have shown that the calcium-sensing receptor (CaSR) mediates the antitumorigenic effects of calcium against colorectal cancer (CRC). Expression of the CaSR in colorectal tumors is often reduced. We have reported previously that silencing of CaSR in CRC is caused in part by methylation of CaSR promoter 2 and lo...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Fetahu IS,Tennakoon S,Lines KE,Gröschel C,Aggarwal A,Mesteri I,Baumgartner-Parzer S,Mader RM,Thakker RV,Kállay E

    更新日期:2016-01-01 00:00:00

  • Tumor-cell killing by MAbs against fucosyl GM1, a ganglioside antigen associated with small-cell lung carcinoma.

    abstract::Monoclonal antibodies (MAbs) reactive with the ganglioside fucosyl GM1 (Fuc-GM1), an antigen associated with small-cell carcinoma of the lung (SCLC), were tested for their ability to mediate tumor-cell killing in vitro in conjunction with humoral and cellular effectors and to inhibit tumor engraftment in nude mice in ...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Brezicka FT,Holmgren J,Kalies I,Lindholm L

    更新日期:1991-12-02 00:00:00

  • MHC-restricted responses of CD8+ and CD4+ T-cell clones from regional lymph nodes of melanoma patients.

    abstract::Regional lymph-node (LN) lymphocytes may constitute an important defence against the spread of human melanoma beyond regional LNs. The present study was directed to clonal analysis of lymphocytes cultured either directly from the LNs or after stimulation in cultures with autologous melanoma (MLTC). T-cell clones deriv...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Chen Q,Hersey P

    更新日期:1992-05-08 00:00:00

  • NF-κB and stat3 transcription factor signatures differentiate HPV-positive and HPV-negative head and neck squamous cell carcinoma.

    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


    authors: Gaykalova DA,Manola JB,Ozawa H,Zizkova V,Morton K,Bishop JA,Sharma R,Zhang C,Michailidi C,Considine M,Tan M,Fertig EJ,Hennessey PT,Ahn J,Koch WM,Westra WH,Khan Z,Chung CH,Ochs MF,Califano JA

    更新日期:2015-10-15 00:00:00

  • Ca2+ and calmodulin are involved in the processes conferring stability to DNA in proliferating neoplastic cells.

    abstract::We have examined, in proliferating neoplastic cells, the effect on DNA of EGTA (a chelator of Ca2+) and W7 (an inhibitor of calmodulin). The treatment results in release of single-stranded DNA fragments (2-10 kb) from pre-labelled HMW DNA. When DNA from synchronized neoplastic cells in S phase is examined, almost all ...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Lönn U,Lönn S

    更新日期:1986-06-15 00:00:00

  • The evolving epidemic of breast cancer in sub-Saharan Africa: Results from the African Cancer Registry Network.

    abstract::Breast cancer (BC) is the leading cause of cancer in sub-Saharan Africa (SSA) with rapidly increasing incidence rates reported in Uganda and Zimbabwe. However, the magnitude of these rising trends in premenopausal and postmenopausal women is unknown in most African countries. We used data from the African Cancer Regis...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Joko-Fru WY,Jedy-Agba E,Korir A,Ogunbiyi O,Dzamalala CP,Chokunonga E,Wabinga H,Manraj S,Finesse A,Somdyala N,Liu B,McGale P,Jemal A,Bray F,Parkin DM

    更新日期:2020-10-15 00:00:00

  • Metastatic tumor cells adhere preferentially to the extracellular matrix underlying vascular endothelial cells.

    abstract::Two metastatic cell lines, mouse B16-Fl melanoma and human Hs939 melanoma, were examined for their abilities to adhere to confluent vascular endothelial cell monolayers and to the underlying endothelial extracellular matrix. Tumor cells attacked slowly to the endothelial cell monolayers while they adhered rapidly to i...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Kramer RH,Gonzalez R,Nicolson GL

    更新日期:1980-11-15 00:00:00

  • Evaluation of circulating EBV microRNA BART2-5p in facilitating early detection and screening of nasopharyngeal carcinoma.

    abstract::Nasopharyngeal carcinoma is an Epstein-Barr Virus (EBV) associated malignancy which is highly prevalent in Southeast Asia. EBV-related antibodies have been widely used as screening markers for early nasopharyngeal carcinoma (NPC) detection. However, due to its low positive predictive rate, it is essential to develop n...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Jiang C,Chen J,Xie S,Zhang L,Xiang Y,Lung M,Kam NW,Kwong DL,Cao S,Guan XY

    更新日期:2018-12-15 00:00:00

  • Expression profiling reveals that methylation of TIMP3 is involved in uveal melanoma development.

    abstract::Uveal melanoma is associated with a high tumor-related mortality due to the propensity to develop metastases. The mechanisms that are responsible for malignant dissemination are largely unknown and need to be explored to facilitate diagnosis and treatment of metastases. To identify molecules involved in dissemination,...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: van der Velden PA,Zuidervaart W,Hurks MH,Pavey S,Ksander BR,Krijgsman E,Frants RR,Tensen CP,Willemze R,Jager MJ,Gruis NA

    更新日期:2003-09-10 00:00:00

  • Combretastatin family member OXI4503 induces tumor vascular collapse through the induction of endothelial apoptosis.

    abstract::The mechanism of tumor cell killing by OXI4503 was investigated by studying vascular functional and morphological changes post drug administration. SCID mice bearing MHEC5-T hemangioendothelioma were given a single dose of OXI4503 at 100 mg/kg. Tumor blood flow, measured by microsphere fluorescence, was reduced by 50%...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Sheng Y,Hua J,Pinney KG,Garner CM,Kane RR,Prezioso JA,Chaplin DJ,Edvardsen K

    更新日期:2004-09-10 00:00:00

  • Sister chromatid exchange and nasopharyngeal carcinoma.

    abstract::Sister chromatid exchange (SCE) is a genetic indicator of DNA damage in mammalian cells and may afford a sensitive monitor to follow genomic instability of some individuals with fragile chromosomal diseases or malignancies. In studies on the effect of dinitrosopiperazine (DNP), aflatoxin B1 (AFB1), methyl-nitro-nitros...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Li GY,Yao KT,Glaser R

    更新日期:1989-04-15 00:00:00

  • Down-regulation of BiP/GRP78 sensitizes resistant prostate cancer cells to gene-therapeutic overexpression of REIC/Dkk-3.

    abstract::We have recently shown that an adenovirus carrying REIC/Dkk-3 (Ad-REIC) exhibits a potent tumor-specific cell-killing function for various human cancers. It has also become evident that some human cancers are resistant to Ad-REIC-induced apoptosis. The aim of the present study was to determine the molecular mechanisms...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Tanimoto R,Sakaguchi M,Abarzua F,Kataoka K,Kurose K,Murata H,Nasu Y,Kumon H,Huh NH

    更新日期:2010-04-01 00:00:00

  • Gefitinib prevents cancer progression in mice expressing the activated rat HER2/neu.

    abstract::We tested the efficacy of gefitinib in the prevention of HER2/neu-mediated breast cancer development in BALB-NeuT transgenic mice. Oral administration of gefitinib to female transgenic mice from 5 to 14 weeks of age reduced tumor multiplicity from 9.6 +/- 0.82 to 0.58 +/- 1.1 (83%). We observed a decrease in the numbe...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Piechocki MP,Dibbley SK,Lonardo F,Yoo GH

    更新日期:2008-04-15 00:00:00

  • Evaluation of adult T-cell leukemia/lymphoma incidence and its impact on non-Hodgkin lymphoma incidence in southwestern Japan.

    abstract::The incidence of adult T-cell leukemia/lymphoma (ATL) and its impact on that of total non-Hodgkin lymphoma (NHL) were evaluated in Nagasaki, an area in southwestern Japan where human T-cell lymphotropic virus type I (HTLV-I) is endemic. The first study area comprised 4 towns located on the K Islands, which had a popul...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Arisawa K,Soda M,Endo S,Kurokawa K,Katamine S,Shimokawa I,Koba T,Takahashi T,Saito H,Doi H,Shirahama S

    更新日期:2000-02-01 00:00:00

  • Impaired general cell-mediated immune functions in vivo and in vitro in patients with nasopharyngeal carcinoma.

    abstract::General cell-mediated immune (CMI) functions in NPC patients were investigated by the in vivo Mantoux and in vitro lymphocyte response to PHA assays. Thirty-eight (50%) of 76 untreated NPC patients were hyporesponsive in the Mantoux assay compared to 27 (25%) of 110 control patients. Forty-three (65.2%) of 66 untreate...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Chan SH,Chew TS,Goh EH,Simons MJ,Shanmugaratnam K

    更新日期:1976-08-15 00:00:00

  • Parity, age at first birth and the risk of carcinoma in situ of the breast.

    abstract::Epidemiological studies of in situ breast cancer are sparse, and the role of reproductive history, an established risk modifier for invasive breast cancer, remains incompletely investigated. To examine possible associations with parity and age at first birth, we undertook a case-control study nested in a nationwide co...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Lambe M,Hsieh CC,Tsaih SW,Ekbom A,Trichopoulos D,Adami HO

    更新日期:1998-07-29 00:00:00

  • The association between markers of tumour cell metabolism, the tumour microenvironment and outcomes in patients with colorectal cancer.

    abstract::Tumour cell anaerobic metabolism has been reported to be a prognostic factor in colorectal cancer. The present study investigated the association between monocarboxylate transporter (MCT) 1, MCT 2, lactate dehydrogenase (LDH) 1 and LDH 5, the tumour microenvironment, and outcome in patients with colorectal cancer. A c...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Roseweir AK,Clark J,McSorley ST,vanWyk HC,Quinn JA,Horgan PG,McMillan DC,Park JH,Edwards J

    更新日期:2019-05-01 00:00:00

  • Expression of activation-induced cytidine deaminase in human hepatocytes during hepatocarcinogenesis.

    abstract::Activation-induced cytidine deaminase (AID) plays a role as a genome mutator in activated B cells, and inappropriate expression of AID has been implicated in the immunopathological phenotype of human B-cell malignancies. Notably, we found that the transgenic mice overexpressing AID developed lung adenocarcinoma and he...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Kou T,Marusawa H,Kinoshita K,Endo Y,Okazaki IM,Ueda Y,Kodama Y,Haga H,Ikai I,Chiba T

    更新日期:2007-02-01 00:00:00

  • Synthesis of a nickel tetracarboranylphenylporphyrin for boron neutron-capture therapy: biodistribution and toxicity in tumor-bearing mice.

    abstract::Nickel-2,3,7,8,12,13,17,18-octaacetic acid-5,10,15,20-tetra-[3-carboranyl-methoxyphenyl]-porphyrin octamethylester (NiTCP) was given in a Cremophor EL, a polyethoxylated castor oil, and propylene glycol emulsion to BALB/c mice bearing transplanted s.c. KHJJ mammary carcinomas. A total dose of 244 microg NiTCP/gram bod...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Miura M,Micca PL,Fisher CD,Heinrichs JC,Donaldson JA,Finkel GC,Slatkin DN

    更新日期:1996-09-27 00:00:00

  • Characteristics of membrane and cytosol forms of the mammary tumor glycoprotein molecule MTGP in human breast carcinoma cell cultures and tumors.

    abstract::The presence, concentration and selected molecular characteristics of the human mammary carcinoma glycoprotein molecule set MTGP, a trace and apparently tumor-specific molecule, were examined in fifteen cell cultures established from mammary carcinomas, tissue from seven mammary carcinomas and control cultures. Both c...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Leung JP,Nelson-Rees WA,Moore GE,Cailleau R,Edgington TS

    更新日期:1981-07-15 00:00:00

  • Tumour angiogenesis factor (TAF) in human and animal tumours.

    abstract::Extracts were made from Walker 256 carcinoma, spontaneous rat mammary adenocarcinoma, Wilms' tumour, human neuroblastoma and human haemangioma. Chromatography of the extracts on Sephadex G-100 yielded four fractions, A, B, C and D. Injection of fractions B and C resulted in the growth of new capillaries in the subcuta...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Phillips P,Steward JK,Kumar S

    更新日期:1976-05-15 00:00:00

  • Genetically predicted circulating concentrations of micronutrients and risk of breast cancer: A Mendelian randomization study.

    abstract::The epidemiological literature reports inconsistent associations between consumption or circulating concentrations of micronutrients and breast cancer risk. We investigated associations between genetically predicted concentrations of 11 micronutrients (beta-carotene, calcium, copper, folate, iron, magnesium, phosphoru...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Papadimitriou N,Dimou N,Gill D,Tzoulaki I,Murphy N,Riboli E,Lewis SJ,Martin RM,Gunter MJ,Tsilidis KK

    更新日期:2021-02-01 00:00:00

  • Microsatellite instability in medullary breast carcinomas.

    abstract::Microsatellite instability (MSI) has been reported to occur in a wide variety of sporadic tumours, such as colorectal and gastric cancers. MSI positivity has been associated with a particular clinico-pathologic profile, including the presence of abundant lymphoid infiltration, poor differentiation and a relatively goo...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Schmitt FC,Soares R,Gobbi H,Milanezzi F,Santos-Silva F,Cirnes L,Costa C,Seruca R

    更新日期:1999-08-27 00:00:00

  • Malignant neoplasms in cyclosporin A-induced autoimmunity (CyA-AI).

    abstract::Lethally X-irradiated LEW rats reconstituted with syngeneic bone marrow and given low-dose Cyclosporine A (CyA) for 5 weeks develop, after withdrawal of CyA, symptoms of disease resembling graft-vs.-host disease (GVHD) as seen after allogeneic bone-marrow transplantation. Symptoms of disease may include acute dermatit...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Wodzig KW,Beijleveld LJ,Damoiseaux JG,Arends JW,van Breda Vriesman PJ

    更新日期:1997-07-29 00:00:00

  • Suppression of rhabdomyosarcoma growth by fumagillin analog TNP-470.

    abstract::The purpose of our study was to investigate a novel therapeutic approach for rhabdomyosarcoma (RMS) in an animal model. The pursuit of new therapeutic modalities for RMS is critically important since this type of tumor is the most common soft tissue sarcoma in children and because patients with metastatic disease may ...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Kalebic T,Tsokos M,Helman LJ

    更新日期:1996-11-27 00:00:00