Abstract:
:The anti-p185(her2/neu) peptidomimetic (AHNP) is a small exo-cyclic peptide derived from the anti-p185(her2/neu) rhumAb 4D5 (h4D5). AHNP mimics many but not all of the antitumor characteristics exhibited by h4D5. However, the pharmacokinetic profiles of AHNP are less than optimal for therapeutic or diagnostic purposes. To improve the binding affinity to p185(her2/neu) and the antitumor efficacy, we have engineered a fusion protein containing AHNP and a nonimmunoglobulin protein scaffold, streptavidin (SA). The recombinant protein, AHNP-SA (ASA) bound to p185(her2/neu) with high affinity, inhibited the proliferation of p185(her2/neu)-overexpressing cells, and reduced tumor growth induced by p185(her2/neu)-transformed cells. These data suggest that the bacterially produced tetrameric ASA can be used as an antibody-surrogate molecule. This class of molecule will play a role in the diagnosis and treatment of p185(her2/neu)-related tumors. Our studies establish a general principle by which a small biologically active synthetic exo-cyclic peptide can be engineered to enhance functional aspects by structured oligomerization and can be produced recombinantly using bacterial expression.
journal_name
Oncogenejournal_title
Oncogeneauthors
Masuda K,Richter M,Song X,Berezov A,Masuda K,Murali R,Greene MI,Zhang Hdoi
10.1038/sj.onc.1209745subject
Has Abstractpub_date
2006-12-14 00:00:00pages
7740-6issue
59eissn
0950-9232issn
1476-5594pii
1209745journal_volume
25pub_type
杂志文章相关文献
ONCOGENE文献大全abstract::P53 wild-type and p53-null or mutant cells undergo a G(2)-phase cell-cycle arrest in response to ionizing radiation (IR). In this study we examined the effect of heat-shock protein 90 (HSP90) inhibitor, geldanamycin (GA), on IR-induced G(2) arrest in human colon adenocarcinoma cells with different p53 status. We show ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2008.172
更新日期:2008-09-18 00:00:00
abstract::Activation of Stat5 by many cytokines implies that it cannot alone insure the specificity of the regulation of its target genes. We have evidenced a physical and functional interaction between members of two unrelated transcription factor families, Ets-1, Ets-2 and Stat5, which could contribute to the proliferative re...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1203542
更新日期:2000-04-20 00:00:00
abstract::The recepteur d'origine nantais (RON) is a receptor tyrosine kinase (RTK) in the scatter factor family, which includes the c-Met receptor. RON exhibits increased expression in a significant number of human breast cancer tissues as well as in many established breast cancer cell lines. Recent studies have indicated that...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2008.383
更新日期:2009-01-15 00:00:00
abstract::DNA damage response (DDR), the guardian of genomic integrity, emerges as an oncogene-inducible biological barrier against progression of cancer beyond its early stages. Recent evidence from both cell culture and animal models as well as analyses of clinical specimens show that activation of numerous oncogenes and loss...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1210881
更新日期:2007-12-10 00:00:00
abstract::PI3K/AKT pathway activation is thought to be a driving force in metastatic melanomas. Members of the pleckstrin homology (PH) domain leucine-rich repeat protein Ser/Thr specific phosphatase family (PHLPP1 and PHLPP2) can regulate AKT activation. By dephosphorylating specific serine residues in the hydrophobic motif, P...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-017-0061-7
更新日期:2018-04-01 00:00:00
abstract::Diffuse intrinsic pontine glioma (or DIPG) are pediatric high-grade gliomas associated with a dismal prognosis. They harbor specific substitution in histone H3 at position K27 that induces major epigenetic dysregulations. Most clinical trials failed so far to increase survival, and radiotherapy remains the most effici...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-019-0884-5
更新日期:2019-09-01 00:00:00
abstract::Interleukin-8 (IL-8), a chemokine implicated in the metastasis and angiogenesis of a variety of cancers, has been reported to be overexpressed in prostate cancer. In this study, we ascribe a new role for IL-8 in prostate cancer progression using LNCaP cells. We demonstrate that IL-8 activates the androgen receptor and...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207344
更新日期:2004-03-18 00:00:00
abstract::Small cell lung cancer (SCLC) is a disease characterized by aggressive clinical behavior and lack of effective therapy. Owing to its tendency for early dissemination, only a third of patients have limited-stage disease at the time of diagnosis. SCLC is thought to derive from pulmonary neuroendocrine cells. Although se...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2012.362
更新日期:2013-07-25 00:00:00
abstract::Constitutively active AR-V7, one of the major androgen receptor (AR) splice variants lacking the ligand-binding domain, plays a key role in the development of castration-resistant prostate cancer (CRPC) and anti-androgen resistance. However, our understanding of the regulatory mechanisms of AR-V7-driven transcription ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-017-0047-5
更新日期:2018-03-01 00:00:00
abstract::Since it is reported that adrenomedullin (AM) upregulated by hypoxia inhibits hypoxic cell death, we examined the effects of AM antagonist (AM C-terminal fragment; AM(22-52)) on the growth of pancreatic cancer cells. We, for the first time, demonstrated that AM antagonist significantly reduced the in vivo growth of th...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206207
更新日期:2003-02-27 00:00:00
abstract::Loss of the DNA mismatch repair (MMR) protein MSH3 leads to the development of a variety of tumors in mice without significantly affecting survival rates, suggesting a modulating role for the MutSβ (MSH2-MSH3) complex in late-onset tumorigenesis. To better study the role of MSH3 in tumor progression, we crossed Msh3(-...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2013.365
更新日期:2014-07-24 00:00:00
abstract::The checkpoint sliding-clamp complex, Rad9/Rad1/Hus1, plays a critical role during initiation of checkpoint signals in response to DNA damage and replication disruption. We investigated the impact of loss of Rad1 on checkpoint function and on DNA replication in mammalian cells. We show that RAD1 is an essential gene f...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207753
更新日期:2004-07-22 00:00:00
abstract::SHP-2 protein tyrosine phosphatase plays an important role in activation of the RAS-dependent signaling. Gain-of-function mutations in the PTPN11 gene, which encodes SHP-2, have been found in the leukemia-prone developmental disorder Noonan syndrome as well as sporadic childhood leukemias, indicating that SHP-2 is a b...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1211019
更新日期:2008-06-05 00:00:00
abstract::Cell to cell communication is vital throughout the development of multicellular organisms and during adult homeostasis. One way in which communication is achieved is through the secretion of signaling molecules that are received by neighboring responding cells. Wnt ligands comprise a large family of secreted, hydropho...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1210053
更新日期:2006-12-04 00:00:00
abstract::The t(12;21) translocation, generating the TEL/AML1 fusion protein, is the most common genetic lesion in childhood cancer. Using a bone marrow transplantation model, we demonstrate that TEL/AML1 expression impinges on normal hematopoietic differentiation, leading to the in vivo accumulation and persistence of an early...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208931
更新日期:2005-11-17 00:00:00
abstract::High frequencies of allelic loss on the short arm of chromosome 3 in small cell lung cancer (SCLC) and a number of other tumors suggest the existence of a tumor suppressor gene(s) within the deleted regions. Two small cell lung cancer lines, NCI H740 and GLC20, have been described which have homozygous deletions in th...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1996-12-05 00:00:00
abstract::The diverse checkpoint responses to DNA damage may reflect differential sensitivities by molecular components of the damage-signalling network to the type and amount of lesions. Here, we determined the kinetics of activation of the checkpoint kinases ATM and Chk2 (the latter substrate of ATM) in relation to the initia...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207986
更新日期:2004-10-07 00:00:00
abstract::The mechanisms involved in the p53-dependent control of gene expression following DNA damage have not been completely elucidated. Here, we show that the p53 C terminus associates with factors that are required for the ultraviolet (UV)-induced inhibition of the mRNA 3' cleavage step of the polyadenylation reaction, suc...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.29
更新日期:2011-07-07 00:00:00
abstract::Increased cancer stem cell content during development of resistance to tamoxifen in breast cancer is driven by multiple signals, including Sox2-dependent activation of Wnt signalling. Here, we show that Sox2 increases and estrogen reduces the expression of the transcription factor Sox9. Gain and loss of function assay...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-018-0656-7
更新日期:2019-04-01 00:00:00
abstract::ETS is a family of transcription factors that contain a highly conserved ETS DNA binding domain. Various members of the ETS family are expressed in cells of hematopoietic lineage. ETS-1, ETS-2 and ERGB/FLI-1 are expressed at high levels in T-lymphocytes. HIV-1 infects T-cells and it has been shown that its LTR contain...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1996-01-04 00:00:00
abstract::Expression level of metastasis-associated protein 1 (MTA1) is closely related to tumor growth and metastasis in various cancers. Although increased expression level of MTA1 was observed in hepatocellular carcinoma (HCC), role of MTA1 complex containing histone deacetylase (HDAC) in hepatitis B virus (HBV)-associated h...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1211000
更新日期:2008-05-29 00:00:00
abstract::P16 was originally discovered by its ability to interact with CDK4 and to specifically inhibit the catalytic activity of the CDK4/D1 kinase. Increased attention has focused on the p16 gene because of its location on chromosome 9p21, a region involved in chromosomal rearrangements in a large number of tumor types. The ...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1995-11-16 00:00:00
abstract::B-cell CLL/lymphoma 6 (BCL6) exerts oncogenic effects in several human hematopoietic malignancies including chronic myeloid leukemia (CML), where BCL6 expression was shown to be essential for CML stem cell survival and self-renewal during imatinib mesylate (IM) treatment. As several lines of evidence suggest that inte...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2017.85
更新日期:2017-08-10 00:00:00
abstract::The phosphatidylinositol 3' kinase (PI3K) pathway is involved in many cellular processes including cell proliferation, survival and glucose transport, and is implicated in various disease states, such as cancer and diabetes. Although there have been numerous studies dissecting the role of PI3K signaling in different c...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2013.44
更新日期:2013-11-21 00:00:00
abstract::Cyr61 is a secreted, cysteine-rich, heparin-binding protein that mediates diverse functions including extracellular matrix formation, differentiation, cell proliferation, adhesion, migration, survival, as well as angiogenesis and tumorigenesis. In this study, we found that Cyr61 gene expression is significantly downre...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208550
更新日期:2005-06-02 00:00:00
abstract::Chromosomal aberrations are a hallmark of human cancers, with complex cytogenetic rearrangements leading to genetic changes permissive for cancer initiation and progression. Protection of Telomere 1 (POT1) is an essential component of the shelterin complex and functions to maintain chromosome stability by repressing t...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2016.405
更新日期:2017-04-06 00:00:00
abstract::One of the hallmarks of malignancy is the polarization of tumor-associated macrophages (TAMs) from a pro-immune (M1-like) phenotype to an immune-suppressive (M2-like) phenotype. However, the molecular basis of the process is still unclear. MicroRNA (miRNA) comprises a group of small, non-coding RNAs that are broadly e...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2013.258
更新日期:2014-06-05 00:00:00
abstract::The regulatory step in ubiquitin (Ub)-mediated protein degradation involves recognition and selection of the target substrate by an E3 Ub-ligase. E3 Ub-ligases evoke sophisticated mechanisms to regulate their activity temporally and spatially, including multiple post-translational modifications, combinatorial E3 Ub-li...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1208614
更新日期:2005-04-18 00:00:00
abstract::Loss of von Hippel Lindau (VHL) protein function is a key driver of VHL diseases, including sporadic and inherited clear cell renal cell carcinoma. Modulation of the proteostasis of VHL, especially missense point-mutated VHL, is a promising approach to augmenting VHL levels and function. VHL proteostasis is regulated ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2016.40
更新日期:2016-09-22 00:00:00
abstract::Genetic mutations in BRCA1, which is crucial for the process of DNA repair and maintenance of genomic integrity, are known to increase markedly the risk of breast and ovarian cancers. Clinical genetic testing has been used to identify new BRCA1 variants; however, functional assessment and determination of their pathog...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-019-0968-2
更新日期:2020-01-01 00:00:00