Abstract:
:To assess the in vivo behavior of cytotoxic agents linked to antibodies, deferoxamine, known to form stable chelates with 67Ga, was conjugated with monoclonal antibodies using three different methods. One method used a homocoupling reagent, glutaraldehyde, whereas two other methods used heterocoupling reagents, N-succinimidyl-3-(2-pyridyldithio)propionate and succinimidyl-6-maleimidohexanoate, linking deferoxamine to antibodies through alkylamine, disulfide, and thioether bonds, respectively. Antibodies were efficiently labeled with 67Ga through chelation with deferoxamine without losing antigen-binding capability. 67Ga-labeled antibodies clearly visualized transplanted tumors in nude mice. However, the biodistribution of radioactivity was markedly different with the coupling methods used for the conjugation of deferoxamine and antibodies. High nonspecific uptake in the liver and spleen was observed with 67Ga-labeled antibodies prepared by the glutaraldehyde method. 67Ga-labeled antibodies linked by thioether bonds demonstrated in vivo stability and the highest tumor:liver ratio, whereas 67Ga-labeled antibodies conjugated with disulfide bonds were rapidly cleared from the circulation. These results indicate that antibody conjugates linked by thioether bonds are a better choice for drug targeting and that 67Ga-labeled antitumor monoclonal antibodies are useful not only for the immunoscintigraphy but also for the quantitative assessment and visualization of the biodistribution of drug-antibody conjugates.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Koizumi M,Endo K,Kunimatsu M,Sakahara H,Nakashima T,Kawamura Y,Watanabe Y,Saga T,Konishi J,Yamamuro Tsubject
Has Abstract,Author List Incompletepub_date
1988-03-01 00:00:00pages
1189-94issue
5eissn
0008-5472issn
1538-7445journal_volume
48pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::Hypoxia in solid tumors is associated with treatment resistance and increased metastatic potential. Although hypoxia has been reported in pancreatic cancer patients, there is little direct evidence that this contributes to their overall poor prognosis. To address this, we examined the associations between hypoxia and ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-10-4049
更新日期:2011-04-15 00:00:00
abstract::The metabolic changes in rat hepatoma cell line, AH70 cells, after coculturing with Kupffer cells were visualized using a silicon-intensified target camera and subsequent processing with a computer-assisted digital imaging processor. In cocultured tumor cells, nonactivated Kupffer cells reduced mitochondrial energizat...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1993-06-01 00:00:00
abstract::Expression of some members of the cadherin family is reduced in several human tumors, and CDH13 (H-cadherin), located on chromosome 16q24.2-3, may function as a tumor suppressor gene. In human tumors, loss of expression of many tumor suppressor genes occurs by aberrant promoter region methylation. We examined the meth...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-06-01 00:00:00
abstract::A genome-wide computational screen was performed to identify tumor-associated alternative RNA splicing isoforms. A BLAST algorithm was used to compare 11,014 genes from RefSeq with 3,471,822 human expressed sequence tag sequences. The screen identified 26,258 alternative splicing isoforms of which 845 were significant...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2003-02-01 00:00:00
abstract::TP53 gene mutation is associated with poor prognosis in breast cancer, but additional biomarkers that can further refine the impact of the p53 pathway are needed to achieve clinical utility. In this study, we evaluated a role for the HDMX-S/FL ratio as one such biomarker, based on its association with other suppressor...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-14-2637
更新日期:2015-02-15 00:00:00
abstract::Progression of the eukaryotic cell division cycle is regulated by a series of structurally related serine/threonine protein kinases known as cyclin-dependent kinases (CDKs). The D-type cyclin-dependent kinases, CDK4 and CDK6, have been strongly implicated in the control of G1 progression and the phosphorylation of the...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1994-12-01 00:00:00
abstract::Effects of calyculin A, a potent inhibitor of protein phosphatases 1 and 2A, on X-ray cell killing and chromatin structure were studied using cultured mammalian cells (BHK21). Calyculin A at concentrations of 2.5-20 nM enhanced X-ray cell killing when exponentially growing BHK21 cells were treated with calyculin A for...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1994-04-15 00:00:00
abstract::Quinocarmycin monicitrate (KW2152) and its analogue, DX-52-1, demonstrated specificity for melanomas in the National Cancer Institute in vitro human tumor cell line drug screen. In contrast to most cell lines, a 50% reduction in tumor cell burden (as measured protein) at the end of a 48-h drug incubation was produced ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-02-15 00:00:00
abstract::Depletion of CD4+CD25+ regulatory T cells (Treg) by treatment with alphaCD25 antibody synergizes with vaccination protocols to engender protective immunity in mice. The effectiveness of targeting CD25 to eliminate Treg is limited by the fact that CD25, the low-affinity interleukin-2 receptor, is up-regulated on conven...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-06-2903
更新日期:2007-01-01 00:00:00
abstract::Understanding the intratumoral heterogeneity of hepatocellular carcinoma is instructive for developing personalized therapy and identifying molecular biomarkers. Here we applied whole-exome sequencing to 69 samples from 11 patients to resolve the genetic architecture of subclonal diversification. Spatial genomic diver...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-16-2822
更新日期:2017-05-01 00:00:00
abstract::The inhibitor of apoptosis proteins (IAPs) are a family of antiapoptotic proteins that bind and inhibit caspases 3, 7, and/or 9, but not caspase 8. Growing evidence also indicates that IAPs also modulate cell division, cell cycle progression, and signal transduction pathways. As our basic understanding of IAPs has inc...
journal_title:Cancer research
pub_type: 杂志文章,评审
doi:10.1158/0008-5472.CAN-04-1918
更新日期:2004-10-15 00:00:00
abstract::Recently, we have shown that the p53 tumor suppressor gene product can inhibit expression of the bcl-2 gene. In this report, we explored the molecular basis for p53-mediated down-regulation of bcl-2 gene expression using a cotransfection approach involving p53 expression plasmids and chloramphenicol acetyltransferase ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1994-06-15 00:00:00
abstract::LEC/chTNT-3, a chemokine fusion protein generated previously in our laboratory, produces a 40-60% reduction in well-established solid tumors of the BALB/c mouse. In this study, CD25(+) T-cell depletion was used in combination with LEC/chTNT-3 treatment to enhance the therapeutic value of this approach. In two tumor mo...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2003-12-01 00:00:00
abstract::5-iododeoxyuridine (IdUrd) is highly effective in inducing the production of endogenous viruses (e.g., RNA-containing murine leukemia virus) from a variety of cell lines that normally do not release such viruses. For the activation of murine leukemia virus by IdUrd, its incorporation into cellular DNA is necessary. We...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1979-05-01 00:00:00
abstract::Previous studies have documented the roles of transport via the reduced folate carrier, retention via polyglutamylation, and increased levels of the target enzyme, dihydrofolate reductase in sensitivity to methotrexate. Recent studies have shown that the mitochondrial enzymes in the cellular metabolism of serine, fola...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-12-3709
更新日期:2013-01-15 00:00:00
abstract::A series of linkage studies was previously conducted to identify quantitative trait loci associated with chemically induced lung tumors. However, little is known of genetic susceptibility to spontaneously occurring lung tumorigenesis (SLT) in mice. In this study, we did a whole-genome linkage disequilibrium analysis f...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-1508
更新日期:2005-09-15 00:00:00
abstract::The data of nine monolayer cultures, 48 multicellular spheroids, and 19 s.c. xenografts of LoVo cells were fitted, on an individual basis, by exponential and Gompertzian equations, respectively. The mean growth parameters alpha 0 (initial growth rate) and beta (retardation factor) of the three experimental systems pre...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-12-01 00:00:00
abstract::Antibodies were produced against 220,000-molecular-weight proteins of Syrian hamster embryo cells. The antiserum containing these antibodies is capable of immunologically staining the surfaces and a fibrillar network around untransformed Syrian hamster embryo cells. The staining is removed by adsorption of the antiser...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1977-09-01 00:00:00
abstract::Although chemoresistance remains a primary challenge in the treatment of pancreatic ductal adenocarcinoma (PDAC), exploiting oxidative stress might offer novel therapeutic clues. Here we explored the potential of targeting cystine/glutamate exchanger (SLC7A11/xCT), which contributes to the maintenance of intracellular...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-18-3855
更新日期:2019-08-01 00:00:00
abstract::3-phosphoinositide-dependent protein kinase-1 (PDK1) plays a pivotal role in coupling growth factor receptor signaling to tumor cell proliferation, survival, and invasion. Protein kinase C (PKC) alpha, but not Akt1, was found previously to be downstream of PDK1-mediated transformation of mammary epithelial cells. To d...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2003-09-01 00:00:00
abstract::Recent clinical trials raised concerns regarding the cardiovascular toxicity of selective cyclooxygenase-2 (COX-2) inhibitors and cyclooxygenase-1 (COX-1) is now being reconsidered as a target for chemoprevention. Our aims were to determine whether selective COX-1 inhibition could delay or prevent cancer development a...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-13-2245
更新日期:2014-01-01 00:00:00
abstract::Membrane type-1 matrix metalloproteinase (MT1-MMP) is a promising drug target in malignancy. The structure of MT1-MMP includes the hemopexin domain (PEX) that is distinct from and additional to the catalytic domain. Current MMP inhibitors target the conserved active site in the catalytic domain and, as a result, repre...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-11-4149
更新日期:2012-05-01 00:00:00
abstract::There is an unmet need for pharmacodynamic and predictive biomarkers for antiangiogenic agents. Recent studies have shown that soluble vascular endothelial growth factor receptor 2 (sVEGFR2), VEGF, and several other soluble factors may be modulated by VEGF pathway inhibitors. We conducted a broad profiling of cytokine...
journal_title:Cancer research
pub_type: 杂志文章,多中心研究
doi:10.1158/0008-5472.CAN-09-2533
更新日期:2010-03-15 00:00:00
abstract::The expression of epidermal growth factor (EGF) receptor was examined immunohistochemically in a total of 122 gastric and 61 colonic carcinomas, out of which 16 gastric and 8 colonic carcinomas were also examined by 125I-labeled EGF binding analysis and Western blotting. The values of EGF binding were 12.68 +/- 1.98 (...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-01-01 00:00:00
abstract::A radioimmunoassay for transforming growth factor alpha (TGF-alpha) using synthetic rat sarcoma transforming growth factor and its rabbit polyclonal antibody has been developed. Using radioimmunoassays, the urinary TGF-alpha and epidermal growth factor (EGF) concentrations in 31 patients with hepatocellular carcinoma ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1987-02-01 00:00:00
abstract::Antiangiogenic therapy is efficacious in metastatic renal cell carcinoma (mRCC). However, the ability of antiangiogenic drugs to delay tumor progression and extend survival is limited, due to either innate or acquired drug resistance. Furthermore, there are currently no validated biomarkers that predict which mRCC pat...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-17-0248
更新日期:2017-08-01 00:00:00
abstract::Increasing evidence points to an active stromal involvement in cancer initiation and progression. Cytokines derived from tumor cells are believed to modulate stromal cells to produce growth and angiogenic factors, which in turn provide the tumor with the necessary microenvironment for expansion and invasion. Transform...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-0444
更新日期:2007-06-15 00:00:00
abstract::We have previously reported that several biological agents, when given simultaneously with cytosine arabinoside or cytoxan, will protect from cytosine arabinoside-induced but not from cytoxan-induced alopecia. In the present study we used the secosteroid 1,25-dihydroxyvitamin D3 in a different timing schedule to prote...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1992-09-15 00:00:00
abstract::Neural stem cells (NSCs) are capable of tracking migrating glioma cells. To exploit this tropism to generate an antitumor T-cell response, particularly against disseminating tumor pockets, we inoculated intracranial glioma-bearing mice with interleukin 12 (IL-12) producing NSCs. Intratumoral therapy with IL-12-secreti...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2002-10-15 00:00:00
abstract::The association of intrauterine exposure to diethylstilbestrol (DES) and the subsequent development of reproductive tract abnormalities in young women has been well documented. Although the incidence of vaginal adenocarcinoma was low in the exposed population, vaginal adenosis, a nonmalignant abnormality, was quite co...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1982-05-01 00:00:00