Abstract：
:5,6-Dimethylxanthenone-4-acetic acid (DMXAA) and combretastatin A4 phosphate (CA-4-P) markedly inhibit tumor blood flow in mice and are both currently in clinical trial. One of the challenges in clinical evaluation of antivascular agents is the monitoring of tumor blood flow inhibition in individual patients. This study investigates, using mouse models, whether a new marker for tissue hypoxia, (99m)technetium-labeled 2,2'-(1,4-diaminobutane)bis(2-methyl-3-butanone) dioxime (99mTc-labeled HL-91; Prognox)] has potential for the scintigraphic monitoring of tumor response to antivascular agents. Determination of radioactivity in dissected tissues 3 h after DMXAA (80 micromol/kg) or CA-4-P (227 micromol/kg) was injected indicated that both drugs inhibited blood flow (86RbCl uptake; 84 and 87%, respectively) and increased 99mTc-labeled HL-91 levels (350 and 300%, respectively) selectively in murine RIF-1 tumors. Planar imaging of 99mTc-labeled HL-91 3 h after DMXAA injection showed a dose-dependent increase in tumor levels above a threshold of 50 micromol/kg; this same threshold was observed for the inhibition of tumor blood flow (determined using Hoechst 33342). DMXAA also inhibited blood flow--and increased 99mTc-labeled HL-91 uptake--in MDAH-MCa-4 mouse mammary carcinomas and in NZMN10 human melanoma xenografts. Whether 99mTc-labeled HL-91 might also be useful as a biomarker for tumor cell killing was investigated by clonogenic assay of surviving cells 15 h after imaging 99mTc-labeled HL-91 in RIF-1 tumors. Log cell kill in individual tumors showed a statistically significant linear correlation (P < 0.001) with 99mTc-labeled HL-91 uptake after 60 micromol/kg (r2 = 0.79) and 70 micromol/kg (r2 = 0.44) but not at 80 micromol/kg DMXAA. The lack of correlation at high doses presumably reflects the insensitivity of the tumor-averaged 99mTc-labeled HL-91 signal to small regions in which tumor blood flow is preserved (which will limit log cell kill). The results indicate the potential of 99mTc-labeled HL-91 for the noninvasive imaging of tumor blood flow inhibition by antivascular drugs in humans.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Siim BG,Laux WT,Rutland MD,Palmer BN,Wilson WRsubject
Has Abstractpub_date
2000-08-15 00:00:00pages
4582-8issue
16eissn
0008-5472issn
1538-7445journal_volume
60pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract：:MLH1 is an integral part of the mismatch repair complex, and the loss of this protein is associated with the acquisition of a mutator phenotype, microsatellite instability, and a predisposition to cancer. Deficiencies in the mismatch repair complex, including the loss of MLH1, result in elevated resistance to specific...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2001-02-15 00:00:00
abstract：:The discovery of somatic mutations in EGFR and development of EGFR tyrosine kinase inhibitors (TKI) have revolutionized treatment for lung cancer. However, resistance to TKIs emerges in almost all patients and currently no effective treatment is available. Here, we show that β-catenin is essential for development of E...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-14-0184
更新日期：2014-10-15 00:00:00
abstract：:5-lodo-2'-deoxyuridine (lUdR) significantly increases the total number of spleen cells on the fourth day after administration of 100 mg/kg in normal C3HeB/FeJ male mice. The number of splenic B-cells [cells sensitive to the cytotoxic activity of a rabbit antiserum to mouse F(ab)2, plus complement] increases on the sam...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1976-01-01 00:00:00
abstract：:Drugs that affect blood flow have been shown to be whole body radiation protectors. Using NG-nitro-L-arginine, a specific inhibitor of nitric oxide synthase, and the NO-releasing agent (C2H5)2N[N(O)NO-]Na+ (DEA/NO), we have studied the ability of NO to modulate whole body radiation toxicity in C3H mice. NG-Nitro-L-arg...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1994-07-01 00:00:00
abstract：:MUC1 is a heterodimeric transmembrane glycoprotein that is overexpressed and aberrantly glycosylated in ductal adenocarcinomas. Differential phosphorylation of the MUC1 cytoplasmic tail (MUC1CT) has been associated with signaling events that influence the proliferation and metastasis of cancer cells. We identified a n...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-06-4647
更新日期：2007-06-01 00:00:00
abstract：:The expression of epidermal growth factor receptor and transglutaminase type I, polyamine (putrescine, spermidine, and spermine) levels, ornithine decarboxylase activity, and micronuclei occurrence were assessed in the 7,12-dimethylbenz(a)anthracene (DMBA)-induced hamster buccal pouch model to elucidate the role and t...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1990-04-15 00:00:00
abstract：:Caveolin-1 (CAV1) is the main structural component of caveolae, which are plasma membrane invaginations that participate in vesicular trafficking and signal transduction events. Although evidence describing the function of CAV1 in several cancer types has recently accumulated, its role in melanoma tumor formation and ...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-10-0900
更新日期：2010-10-01 00:00:00
abstract：:Identification of the molecular mechanism of action (MoA) of bioactive compounds is a crucial step for drug development but remains a challenging task despite recent advances in technology. In this study, we applied multidimensional proteomics, sensitivity correlation analysis, and transcriptomics to identify a common...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-19-2069
更新日期：2020-04-01 00:00:00
abstract：:PARP-1 is a nuclear protein that has important roles in maintenance of genomic integrity. During genotoxic stress, PARP-1 recruits to sites of DNA damage where PARP-1 domain architecture initiates catalytic activation and subsequent poly(ADP-ribose)-dependent DNA repair. PARP-1 inhibition is a promising new way to sel...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-13-1701
更新日期：2014-01-01 00:00:00
abstract：:Osteoprotegerin (OPG), a novel, secreted tumor necrosis factor receptor family member that inhibits osteoclast formation and activity was examined for its activity in a syngeneic tumor model of humoral hypercalcemia of malignancy. Normal mice bearing Colon-26 tumors develop increases in both parathyroid hormone-relate...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2000-02-15 00:00:00
abstract：:The effects of in vivo administration of a pharmacologically toxic dose of the lipophilic cationic compound, MKT-077, were investigated in selected vital organs of the rat. MKT-077 (15 mg/kg body weight), administered by bolus i.v. injection every day for 5 days, did not detectably influence rat heart and kidney mitoc...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1996-02-01 00:00:00
abstract：:Proteasome inhibitors sensitize tumor cells to DNA-damaging agents, including ionizing radiation (IR), and DNA cross-linking agents (melphalan and cisplatin) through unknown mechanisms. The Fanconi anemia pathway is a DNA damage-activated signaling pathway, which regulates cellular resistance to DNA cross-linking agen...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-07-1015
更新日期：2007-08-01 00:00:00
abstract：:The combinations of amphotericin B (AmB) with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) or 2-cyclohexyl isocyanate, the carbamoylating decomposition product of CCNU, were more potent in lysing HL-60 cells than the combinations of AmB with 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) or 2-chloroethyl isocyana...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1990-06-01 00:00:00
abstract：:Peroxisome proliferator-activated receptor (PPAR) gamma is an important signaling molecule in cells of mesenchymal origin, inducing differentiation and regulating cell proliferation in several cell types such as vascular smooth muscle cells. Leiomyomas arise from smooth muscle cells of the uterine myometrium with an i...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2003-03-15 00:00:00
abstract：:Pharmacokinetic studies of 5-fluorouracil (5-FUra) were performed on 18 patients divided into three groups: seven patients were given 5-FUra i.v. by rapid injection; five patients received the drug p.o.; and six patients were treated by continuous i.v. infusion for 96 hr. The results showed rapid i.v. injection to be ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1980-07-01 00:00:00
abstract：:Phorbol diester (PDE) tumor promoters affect cells by interacting with specific receptors on the plasma membrane. Cells are known to regulate their receptor populations in response to many external and internal stimuli, including differentiation. The human promyelocytic leukemia cell line HL-60, which can be induced b...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1986-08-01 00:00:00
abstract：:The majority of BRCA1-associated breast cancers are basal cell-like, which is associated with a poor outcome. Using a spontaneous mouse mammary tumor model, we show that platinum compounds, which generate DNA breaks during the repair process, are more effective than doxorubicin in Brca1/p53-mutated tumors. At 0.5 mg/k...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-07-5480
更新日期：2008-05-01 00:00:00
abstract：:S49 cyc- lymphoma cells contain a mutation resulting in loss of a functional guanine nucleotide regulatory protein rendering their adenylate cyclase refractory to most stimuli. S49 wild-type and cyc- clones were used in the present study to investigate the possible association of altered cAMP metabolism with tumorigen...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1988-02-01 00:00:00
abstract：:The influence of pretreatment with piperonylbutoxide (PIP) on the biological effects of N-nitrosodiethylamine (DEN) in vivo in Syrian golden hamsters was investigated. PIP pretreatment significantly reduced covalent binding of N-[ethyl-1-14C]DEN to tissue macromolecules in trachea, lung, and liver, while it did not ch...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1985-06-01 00:00:00
abstract：:Multidrug-resistant cells are thought to maintain low intracellular cytotoxic drug concentration though the active efflux of drugs across the cell membrane. It is presently believed that P-glycoprotein mediates this energy-dependent drug efflux by interacting directly with various lipophilic compounds. In this report,...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1993-12-15 00:00:00
abstract：:Immunotoxins directed against human transferrin receptor have been evaluated in a nude mouse model of human malignant mesothelioma. Immunotoxins were constructed by linking ricin A chain to murine monoclonal antibodies reactive with the human transferrin receptor. A chain was obtained either by isolation from the pare...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1987-08-15 00:00:00
abstract：:The main objective of the present study was to sequentially analyze growth and morphological characteristics of aberrant crypt foci (ACF) in the rat colon. Sprague-Dawley rats were given a single injection of a carcinogenic dose of 1,2-dimethylhydrazine-HCl and at varying time points ranging from 2 to 57 weeks, groups...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1991-10-01 00:00:00
abstract：:Stomach cancer incidence rates vary by ethnic group in New Mexico, with American Indians and Hispanic Whites at higher risk than the state's non-Hispanic White population. To further characterize the descriptive epidemiology of this disease in New Mexico, we investigated temporal trends in stomach cancer mortality and...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1989-03-15 00:00:00
abstract：:Breast carcinomas < or = 1 cm in size (T1a,b) are being detected more frequently as a result of screening. Because traditional prognostic parameters are either lacking (tumor size) or rare (nodal metastases), a marker(s) is needed to identify the subset of patients who could benefit from adjuvant therapy. A retrospect...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1997-04-01 00:00:00
abstract：:Incubation of taxol with human hepatic microsomal fractions or freshly isolated human liver slices yields three metabolite high performance liquid chromatography peaks, metabolite A, metabolite B, and 6 alpha-hydroxytaxol. These metabolites are formed in patients given taxol, with 6 alpha-hydroxytaxol formation repres...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1994-08-01 00:00:00
abstract：:Perineural invasion is a common feature of pancreatic ductal adenocarcinoma (PDAC). Here, we investigated the effect of perineural invasion on the microenvironment and how this affects PDAC progression. Transcriptome expression profiles of PDAC tissues with different perineural invasion status were compared, and the i...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-19-2689
更新日期：2020-05-15 00:00:00
abstract：:The altered gene expression seen in cancer could relate to differences in nonhistone chromatin proteins between normal and malignant tumor cells. Phenol-soluble nonhistone chromatin proteins were isolated from human normal and leukemic (chronic lymphocytic leukemia) B-cells, as well as long-term cultured human B-lymph...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1984-05-01 00:00:00
abstract：:The EphA2 receptor tyrosine kinase is found at low levels on nontransformed adult breast epithelial cells but is frequently overexpressed on aggressive breast cancer cells. Recent studies have documented an inverse relationship between EphA2 and estrogen receptor expression in breast cancer cell lines. In our present ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2003-06-15 00:00:00
abstract：:Administration of alpha/beta-interferon (IFN) exerts a marked antitumor effect in DBA/2 mice given injections i.v. of large numbers of IFN-alpha/beta-resistant erythroleukemia cells (FLC). To investigate the possible mechanisms of FLC tumor inhibition in the liver of interferon-treated mice, we developed an in vitro m...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1990-06-15 00:00:00
abstract：:Host resistance to tumor growth was studied in athymic nude mice of C57BL background. Animals were pretreated in the left hind leg by local hyperthermia, local X-irradiation, or combined local hyperthermia and X-irradiation. Twenty-four hr posttreatment, the animals were inoculated with the metastatic Lewis lung carci...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1979-03-01 00:00:00
