Pharmacokinetic evaluation of toremifene and its clinical implications for the treatment of osteoporosis

Gennari, Luigi; Merlotti, Daniela; Stolakis, Konstantinos; Nuti, Ranuccio

doi:10.1517/17425255.2012.665873

Cited by 7 publications

(4 citation statements)

References 53 publications

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“…It is notable that the unique pharmacokinetic characteristics make tamoxifen more advantageous in gallbladder cancer treatment . Tamoxifen metabolites 4‐hydroxytamoxifen and N‐desmethyl‐4‐hydroxytamoxifen, which possess a much stronger ER inhibitory activity, could be secreted in bile and participate in enterohepatic circulation . The bile infiltrating environment of GBC provides another platform for tamoxifen metabolites to reach tumour.…”

Section: Discussionmentioning

confidence: 99%

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Tamoxifen inhibits cell proliferation by impaired glucose metabolism in gallbladder cancer

Huang

Wang

Chen

et al. 2019

J Cellular Molecular Medi

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Gallbladder cancer (GBC) is the leading malignancy of biliary system showing refractory chemoresistance to current first-line drugs. Growing epidemiological evidences have established that the incidence of GBC exhibits significant gender predominance with females two-threefold higher than males, suggesting oestrogen/oestrogen receptors (ERs) signalling might be a critical driver of tumorigenesis in gallbladder. This study aims to evaluate the antitumour activity of tamoxifen (TAM), a major agent of hormonal therapy for breast cancer, in preclinical GBC model. Quantitative real-time PCR was used to investigate mRNA levels. Protein expression was measured by immunohistochemistry and Western blot. Glycolytic levels were measured by glucose consumption and lactic acid measurement. The antitumour activity of TAM alone or with cisplatin was examined with CCK8 assay, colony formation, flow cytometry and in vivo models. The results revealed that ERɑ expression was higher in GBC tissues and predicted poor clinical outcomes. TAM was showed effective against a variety of GBC cell lines. Mechanical investigations revealed that TAM enabled potent reactive oxygen species (ROS) production by reduced nuclear factor Nrf2 expression and its target genes, leading to the activation of AMPK, which subsequently induced impaired glycolysis and survival advantages. Notably, TAM was demonstrated to sensitize GBC cells to cisplatin (CDDP) both in vitro and in vivo. In agreement with these findings, elimination of oestrogens by ovariectomy in nude mice prevented CDDP resistance. In summary, these results provide basis for TAM treatment for GBC and shed novel light on the potential application of endocrine therapy for patients with GBC.

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Section: Discussionmentioning

confidence: 99%

“…45 Tamoxifen metabolites 4-hydroxytamoxifen and N-desmethyl-4hydroxytamoxifen, which possess a much stronger ER inhibitory activity, 46 could be secreted in bile and participate in enterohepatic circulation. [47][48][49] The bile infiltrating environment of GBC provides another platform for tamoxifen metabolites to reach tumour.…”

Section: Discussionmentioning

confidence: 99%

Tamoxifen inhibits cell proliferation by impaired glucose metabolism in gallbladder cancer

Huang

Wang

Chen

et al. 2019

J Cellular Molecular Medi

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“…TOR differs from tamoxifen’s structure in only a single chloride atom on its side group; a chloride atom substituted for a hydrogen atom in the ethyl group attached to part of the ethylene bond 88. TOR functions in a similar way to other Type I SERMs, displaying a higher affinity for ERα (about 5% of that of estradiol) than ERβ 89.…”

Section: Triphenylethylene Sermsmentioning

confidence: 99%

Selective estrogen receptor modulators: tissue specificity and clinical utility

Martinkovich¹,

Shah²,

Planey³

et al. 2014

CIA

124

103

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Selective estrogen receptor modulators (SERMs) are a diverse group of nonsteroidal compounds that function as agonists or antagonists for estrogen receptors (ERs) in a target gene-specific and tissue-specific fashion. SERM specificity involves tissue-specific expression of ER subtypes, differential expression of co-regulatory proteins in various tissues, and varying ER conformational changes induced by ligand binding. To date, the major clinical applications of SERMs are their use in the prevention and treatment of breast cancer, the prevention of osteoporosis, and the maintenance of beneficial serum lipid profiles in postmenopausal women. However, SERMs have also been found to promote adverse effects, including thromboembolic events and, in some cases, carcinogenesis, that have proven to be obstacles in their clinical utility. In this review, we discuss the mechanisms of SERM tissue specificity and highlight the therapeutic application of well-known and emergent SERMs.

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“…The majority of the toremifene dose is excreted as metabolites in feces. The long terminal half-life of oral toremifene may be due to both plasma protein binding and enterohepatic recirculation [182,183].…”

Section: (4) Cationic Amphiphilesmentioning

confidence: 99%

Human Ebola virus infection in West Africa: a review of available therapeutic agents that target different steps of the life cycle of Ebola virus

Lai

Cheng

2014

Infect Dis Poverty

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The recent outbreak of the human Zaire ebolavirus (EBOV) epidemic is spiraling out of control in West Africa. Human EBOV hemorrhagic fever has a case fatality rate of up to 90%. The EBOV is classified as a biosafety level 4 pathogen and is considered a category A agent of bioterrorism by Centers for Disease Control and Prevention, with no approved therapies and vaccines available for its treatment apart from supportive care. Although several promising therapeutic agents and vaccines against EBOV are undergoing the Phase I human trial, the current epidemic might be outpacing the speed at which drugs and vaccines can be produced. Like all viruses, the EBOV largely relies on host cell factors and physiological processes for its entry, replication, and egress. We have reviewed currently available therapeutic agents that have been shown to be effective in suppressing the proliferation of the EBOV in cell cultures or animal studies. Most of the therapeutic agents in this review are directed against non-mutable targets of the host, which is independent of viral mutation. These medications are approved by the Food and Drug Administration (FDA) for the treatment of other diseases. They are available and stockpileable for immediate use. They may also have a complementary role to those therapeutic agents under development that are directed against the mutable targets of the EBOV.Electronic supplementary materialThe online version of this article (doi:10.1186/2049-9957-3-43) contains supplementary material, which is available to authorized users.

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Pharmacokinetic evaluation of toremifene and its clinical implications for the treatment of osteoporosis

Cited by 7 publications

References 53 publications

Tamoxifen inhibits cell proliferation by impaired glucose metabolism in gallbladder cancer

Tamoxifen inhibits cell proliferation by impaired glucose metabolism in gallbladder cancer

Selective estrogen receptor modulators: tissue specificity and clinical utility

Human Ebola virus infection in West Africa: a review of available therapeutic agents that target different steps of the life cycle of Ebola virus

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