Abstract:
:Knowledge of the presence and extent of disease plays a major role in clinical management of prostate cancer, as it provides meaningful information as to which therapy to choose and who might benefit from this therapy. The wide expression of androgen receptor (AR) in primary and metastatic prostate tumors offers a cellular target for receptor-mediated imaging of prostate cancer. In our previous study, a non-steroidal AR ligand, S-26 [S-3-(4-fluorophenoxy)-2-hydroxy-2-methyl-N-(4-cyano-3-iodophenyl)-propionamide] showed promising in vitro pharmacological properties as an AR-mediated imaging agent, with high AR binding affinity and AR specificity. The overall goal of this study was to characterize the in vivo metabolic and biodistribution profile of S-26 in rats. Non-compartmental pharmacokinetic analysis of S-26 in rat plasma showed that clearance (CL), volume of distribution (Vd(ss)), and half-life (T(1/2)) of S-26 were 0.30 + or - 0.07 l/h/kg, 1.44 + or - 0.33 l/kg, and 4 h, respectively, after intravenous (i.v.) administration. Dose proportionality (1, 10 and 30 mg/kg) studies suggested that the pharmacokinetics of S-26 are dose-independent. The plasma concentrations of all 3 doses were further simultaneously fitted with a two-compartmental model and the results were similar to those obtained from non-compartmental analysis. Biodistribution studies using (125)I-labeled S-26 indicated that it did not specifically target AR-rich tissue (e.g. prostate). A substantial amount of radioactivity recovered from thyroid gland indicated the release of free iodine. In metabolism studies, unchanged S-26 and its metabolites were detected in rat urine and fecal samples. Oxidation, de-iodination, hydrolysis, and sulfate conjugation were the major metabolic pathways of S-26 in rats, with de-iodination representing a unique metabolic pathway of S-26 among other selective androgen receptor modulators. In conclusion, the extensive plasma clearance and de-iodination of S-26 likely contribute to its lack of AR tissue selectivity in vivo. Future studies using metabolically stable ligands with less lipophilicity and higher AR binding affinity may represent a promising and rational approach for AR-mediated imaging.
journal_name
Int J Oncoljournal_title
International journal of oncologyauthors
Yang J,Wu Z,Wu D,Darby MV,Hong SS,Miller DD,Dalton JTsubject
Has Abstractpub_date
2010-01-01 00:00:00pages
213-22issue
1eissn
1019-6439issn
1791-2423journal_volume
36pub_type
杂志文章abstract::Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is one of the most promising anti-cancer agents, but some tumor types develop resistance to TRAIL. Here, we report that chetomin, an inhibitor of hypoxia-inducible factors, is a potent enhancer of TRAIL-induced apoptosis. TRAIL or chetomin alone weakly in...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2010.874
更新日期:2011-02-01 00:00:00
abstract::Radioiodinated meta-iodobenzylguanidine (MIBG), an analogue of norepinephrine, has been used in management of neuroendocrine tumors. Recent studies reveal that distribution of radioiodinated MIBG in animals depends on the specific activity of this radiopharmaceutical. In order to clarify the effect of specific activit...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.10.4.815
更新日期:1997-04-01 00:00:00
abstract::High-mobility group AT-hook protein 2 (HMGA 2) is a transcription factor associated with malignancy and poor prognosis in a variety of human cancers. We correlated HMGA 2 expression with clinical parameters, survival, and O-6-methylguanine-DNA methyltransferase methylation status (MGMT) in glioblastoma patients. HMGA ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2016.3397
更新日期:2016-04-01 00:00:00
abstract::Induction chemotherapy provides an excellent model for evaluation of potential predictive factors. We studied expression of SBR grade, estrogen (ER) and progesterone (PR) receptors, HER2, Ki67 and P53 on core biopsies before and after chemotherapy in a series of 115 patients, who received anthracycline-based induction...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2003-06-01 00:00:00
abstract::Despite attempts to use multiple drug combinations that include gemcitabine (GEM), there is very little evidence that these combination regimens are superior to the single use of this agent. We therefore investigated the suppressive effect of the combination of systemically administered GEM and locally administered in...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2008-07-01 00:00:00
abstract::CA IX is a tumor-associated transmembrane isoform of the carbonic anhydrase with a high enzyme activity and a functional involvement in the pH regulation and cell adhesion. Expression of CA9 gene in tumor cells is principally regulated by the high cell density and the hypoxia-related VHL-HIF pathway. In renal cell car...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2005-04-01 00:00:00
abstract::Recently, the compilation of massive amounts of genetic and genomic information on a wide variety of human cancer types, collectively known as The Cancer Genome Atlas (TCGA), has revealed a wealth of descriptive classification schemes both within and between different types and sources of cancer. In endometrial cancer...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2020.5139
更新日期:2020-12-01 00:00:00
abstract::Pancreatic neuroendocrine neoplasms (p-NENs) are slowly growing tumors with frequent liver metastasis. There is a variety of approaches to treat non-functional p-NENs with synchronous liver metastasis (LM) which complicates the determination of optimal treatment. Based on updated literature review, we discussed the tr...
journal_title:International journal of oncology
pub_type: 共识发展会议,杂志文章
doi:10.3892/ijo.2016.3711
更新日期:2016-11-01 00:00:00
abstract::The proper structure of the extracellular matrix, in particular of the basement membrane and the adjacent interstitial matrix, are essential prerequisites for a proper function of tissues. Invasive growth in malignant tumors is associated with a destruction of various matrix structures. Due to extensive recent analyse...
journal_title:International journal of oncology
pub_type: 杂志文章,评审
doi:10.3892/ijo.18.4.669
更新日期:2001-04-01 00:00:00
abstract::Triple negative breast cancer (TNBC) patients cannot be treated with endocrine therapy or targeted therapies due to lack of related receptors. These patients overexpress the epidermal growth factor receptor (EGFR), but are resistant to tyrosine kinase inhibitors (TKIs) and anti-EGFR therapies. Mechanisms suggested for...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2014.2805
更新日期:2015-03-01 00:00:00
abstract::Previously we demonstrated that a mutated human prolactin (hPRL) with a single amino acid substitution at position 129 (hPRL-G129R) was able to inhibit human breast cancer cell proliferation via the induction of apoptosis. In this study, we report the in vivo anti-tumor effects of hPRL-G129R in nude mice bearing human...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.20.4.813
更新日期:2002-04-01 00:00:00
abstract::Cisplatin-resistance has become a major impediment in the medical treatment of cancers such as osteosarcoma, the most common primary malignancy of bone. Since lysophosphatidic acid acyltransferase β (LPAATβ) was reported to be critically involved in osteosarcoma, our study investigated the role of LPAATβ in human oste...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2016.3820
更新日期:2017-02-01 00:00:00
abstract::The development of carcinoma is associated with alterations in the expression of many cell adhesion molecules. Syndecan-1 is a cell surface proteoglycan that binds cells to the extracellular matrix and changes its expression following malignant transformation in some tumors. Our purpose was to examine the pattern of s...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2002-01-01 00:00:00
abstract::On the basis of immunological results, it is not in doubt that the immune system is able to recognize and eliminate transformed cells. A plethora of studies have investigated the immune system of patients with cancer and how it is prone to immunosuppression, due in part to the decrease in lymphocyte proliferation and ...
journal_title:International journal of oncology
pub_type: 杂志文章,评审
doi:10.3892/ijo.2018.4283
更新日期:2018-04-01 00:00:00
abstract::TGF-beta1 stimulates proliferation of WI38 human embryo fibroblasts but inhibits that of their SV40-transformed counterparts, VA13 cells. Protein expression levels of cyclins A, D1, E and that of cdk2 and cdk4 were not affected by TGF-beta1 in either of these cells. However, TGF-beta1-treatment increases cdk2 kinase a...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.14.5.905
更新日期:1999-05-01 00:00:00
abstract::Cognate interactions between naïve tumor antigen (TA)-specific T cells and TA-presenting dendritic cells (DCs) are facilitated by secondary lymphoid organs such as lymph nodes or the spleen. These can result either in TA-specific tolerance or, depending on environmental costimulatory signals, in TA-specific immune res...
journal_title:International journal of oncology
pub_type: 杂志文章,评审
doi:10.3892/ijo.2015.3197
更新日期:2015-12-01 00:00:00
abstract::Bovine lactoferricin (LfcinB) is a cationic antimicrobial peptide that selectively induces apoptosis in several different types of human cancer cells. However, the potential use of LfcinB as an anticancer agent is presently limited by the need for relatively high concentrations of the peptide to trigger apoptosis. Cer...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2008-03-01 00:00:00
abstract::Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is promising for cancer treatment owing to its selective cytotoxicity against malignant cells. However, some cancer cell types, including malignant melanoma cells, are resistant to TRAIL-induced apoptosis. Therefore, dr...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2012.1483
更新日期:2012-08-01 00:00:00
abstract::Changes in the promoter methylation of hTERT, the gene that encodes telomerase, a ribonucleoprotein responsible for replacing telomeric repeats, have been demonstrated in differentiating cells where hTERT is inhibited, suggesting epigenetic regulation of hTERT. All-trans retinoic acid (ATRA) induces differentiation in...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2008-03-01 00:00:00
abstract::Progression of oral carcinomas associates with aberrant activation and inactivation of molecules that work in established or unknown pathways. Although mucosa‑associated lymphoid tissue 1 (MALT1) expressed in normal oral epithelium is inactivated in the aggressive subset of carcinomas with worse prognosis, phenotypic ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2013.1990
更新日期:2013-09-01 00:00:00
abstract::CDH13 (H-cadherin) is a member of the cadherin superfamily, which plays an important role in cell recognition and adhesion. We examined the expression and methylation status of the CDH13 gene in diffuse large B cell lymphomas (B-DLCLs). We found decreased expression of the CDH13 gene in all of 6 hematopoietic cell lin...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2004-09-01 00:00:00
abstract::Acquirement of multi-drug resistance by tumor cells represents a major obstacle in the management of prostate cancer. Such resistance was demonstrated in the androgen-independent DU-145 cells in response to paclitaxel and the mechanisms by which these cell develops resistance was not understood. The objective of this ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2003-08-01 00:00:00
abstract::MicroRNAs (miRNAs) are a large family of small, non-coding RNAs that play a pivotal role in tumorigenesis. miR‑34a, which is a member of the miR-34 family, is a downstream target of p53. Increasing evidence shows that miR-34a dysregulation may contribute to tumor development and progression in numerous cancers, includ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2017.4015
更新日期:2017-07-01 00:00:00
abstract::B7-H4 is a transmembrane protein which is a member of the B7 superfamily. It is overexpressed in various types of cancer, including gastric cancer. However, the effects of B7-H4 on the tumorigenicity of gastric cancer and the underlying mechanisms have not yet been fully explored. Thus, the aim of this study was to ex...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2018.4274
更新日期:2018-04-01 00:00:00
abstract::We have recently demonstrated in a mouse renal adenocarcinoma tumor system that the antitumor effect of adriamycin (ADM) in combination with interleukin-2 (IL2) is superior to treatment with either ADM or IL2 alone. Based on this observation we postulated that modulation of host's immune competence by ADM and/or IL2 m...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:1992-12-01 00:00:00
abstract::RhKGF is developed for prevention and treatment of chemotherapy- and radiation-induced epithelial damage in cancer patients. Little information exists on growth modulation of malignant cells by KGF. We have tested the anchorage-independent clonal growth of 35 human tumor and 22 lymphoma and leukemia cell lines in semi...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2004-10-01 00:00:00
abstract::Tumor necrosis factor α induced protein 3 (TNFAIP3) is a protein that is induced by TNF-mediated NF-κB activation and has a dual function in regulating NF-κB. TNFAIP3 is associated with inflammatory carcinogenesis in many cancer types. However, the clinical significance of TNFAIP3 expression and function in esophageal...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2017.3869
更新日期:2017-03-01 00:00:00
abstract::Insulin-like growth factor-II (IGF-II)/IGF2R signaling plays a pivotal role in cell growth, migration and differentiation in many malignancies. An individual with high IGF-II expression levels has a high risk of developing cancer, but IGF2R is often considered to be a tumor suppressor. To date, little has been reporte...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2014.2512
更新日期:2014-09-01 00:00:00
abstract::Aberrant glycosylation is a universal feature of cancer cells, and certain glycan structures are well-known markers for tumor progression. Availability and composition of sugars in the microenvironment may affect cell glycosylation. Recent studies of human breast tumor cell lines indicate their ability to take up and ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo_00000710
更新日期:2010-09-01 00:00:00
abstract::Cancer stem cells (CSCs), which have the potential for self-renewal, differentiation and de-differentiation, undergo epigenetic, epithelial-mesenchymal, immunological and metabolic reprogramming to adapt to the tumor microenvironment and survive host defense or therapeutic insults. Intra-tumor heterogeneity and cancer...
journal_title:International journal of oncology
pub_type: 杂志文章,评审
doi:10.3892/ijo.2017.4129
更新日期:2017-11-01 00:00:00