An Estrogen Receptor Assay Is Best Described As A Test For

An Estrogen Receptor Assay Is Best Described As A Test For-14
Taxanes are a family of natural products with a broad spectrum of anticancer activity.This activity is mediated by interaction with the taxane site of beta-tubulin, leading to microtubule stabilization and cell death.For example, the two hydroxyl phenyl rings of SERMs and paclitaxel were found in a similar position.

Although paclitaxel and the second-generation docetaxel (Taxotere, Aventis, Bridgewater, NJ) are two of the most successful chemotherapies for the treatment of breast, ovarian, lung carcinomas, and other malignancies, their clinical use is hampered by drug resistance, hypersensitivity reaction to the drug vehicle, dose-limiting toxicity associated with neurotoxicity, myelosuppression, and other severe side effects.

Furthermore, most taxane drugs, both semisynthetic analogues of paclitaxel and natural products, have higher molecular weight than paclitaxel, are impractical for oral administration, and offer no improvement in clinical performance over the original compounds.

To quantify the binding site similarity, shared microenvironments between two protein-ligand pockets were used to determine a Pocket Feature Score (PFS), which indicates the likelihood that the ligand from the screened protein pockets will interact with the taxane site.

In silico binding site similarity screen identifies tubulin-ER cross-reactivity.

Evaluation of nine selective estrogen receptor modulators (SERMs) via cellular and biochemical assays confirms taxane site interaction, microtubule stabilization, and cell proliferation inhibition.

Our study demonstrates that SERMs can modulate microtubule assembly and raises the possibility of an estrogen receptor-independent mechanism for inhibiting cell proliferation..Therefore, identifying a generation of synthetic taxanes remains an attractive strategy for improving the current state of cancer treatment, especially if molecules with optimal pharmacokinetic properties and resistance profiles could be developed rapidly.A promising strategy for anticancer drug discovery is drug repurposing, also known as drug repositioning, in which a known drug can be repurposed to address cancer indications based on previously off-target interactions.Microtubules transport and position cellular components in interphase and form the mitotic spindle in mitosis.Microtubule arrays in both cases are highly dynamic, with the assembly and disassembly of the polymer regulated by the intrinsic tubulin GTP hydrolysis and microtubule-associated proteins.Target enrichment analysis showed that among the 36 ligands, the most abundant protein target families with sites similar to the taxane pocket were ERs (12), beta-tubulins (4), MAPK14 kinases (4), dihydroorotate dehydrogenases (DHODHs) (3), and 13 other proteins (Fig. The 12 ER ligands identified from our binding site similarity screen were predominantly SERMs, which are partial agonists of the ERs (Supplementary Data 2).Several SERMs are analogues of raloxifene (RAL) and tamoxifen (TAM), which are FDA-approved drugs for the treatment and prevention of osteoporosis, and for the reduction of breast cancer risk in postmenopausal woman.a The computational workflow of identifying and validating ligands binding to the taxane pocket of microtubules.Microenvironments of the taxane pocket were compared to a database of protein pocket microenvironments bound to small molecule ligands.The recent wide availability of protein crystal structures from the protein data bank (PDB) offers potential opportunities to discover biological activities of known drugs based on detailed structural knowledge of the protein-ligand interaction.Here, we use a structure-based drug repurposing strategy to discover taxane site modulators by evaluating the similarity between the beta-tubulin taxane site and pockets of drug-like compounds.


Comments An Estrogen Receptor Assay Is Best Described As A Test For

  • Prediction of Low versus High Recurrence Scores in Estrogen.

    Mar 3, 2016. Most patients with early-stage stage I or II estrogen receptor ER. Calif genomic assay has been used to guide prognostic estimation and treatment decisions 2. With Oncotype DX test recurrence scores ODRS, a sample of. The receptor ER, PR, and HER2 status of the tumors is described in.…

  • Estrogen receptor values in patients with benign breast disease

    Patients with estrogen receptor positive tumors had a mean age of. 26.9 years compared to. estrogen receptor assay was taken to be equal or greater than 10. value for menopausal status defined by the presence or absence. best separation between hormone responsive. Rank-Sum test adjusted for ties. This latter.…

  • Study of Interlaboratory Reliability and Reproducibility of.

    Estrogen and Progesterone Receptor Assays in Europe. specificity, sensitivity, and reproducibility of the tests on. strate ER and/or PR and to return the best stained slides. ER/PR expression of tumors is described in terms of proportion of invasive nuclei staining % and average staining intensity +, ++, +++.…

  • Pocket similarity identifies selective estrogen receptor. - Nature

    Mar 4, 2019. Evaluation of nine selective estrogen receptor modulators SERMs via cellular and. were identified and ligands were tested using in vitro tubulin polymerization assay and in. The cells were fixed and stained as described. conformation pose within the receptor site points to identify the best pose.…

  • Predictive Endocrine Testing in the 21st Century Using in Vitro.

    Jun 24, 2014. The results from the in vitro assays were used to create an ER Interaction Score. A more complete description of the Novascreen assays and.…

  • Estrogen Receptor Status by Immunohistochemistry Is.

    Superior to the Ligand-Binding Assay for Predicting. Response to. previously described. J3 Because of. models for the mUltiple significance testing used to define the ER cut point, the. best cut point THe score 2 was highly significant.…

  • Estrogen Receptor Expression Is Associated with DNA Repair.

    Mar 31, 2016. Adding a DNA repair capacity test to hormone receptor testing may provide. Best Practices in Research Reporting · Human Subjects Research · Animal. ER+/HER2- tumors are heterogeneous, incompletely defined, and clinically. Although the DRC assay is currently used primarily as a method of.…

  • Multi-gene assays effect on chemotherapy use, toxicity and.

    Jan 21, 2019. Relative to no testing, chemotherapy use was higher with 12-gene and. for women with estrogen receptor-positive ER+ early stage breast cancer is to. is defined by the line between no MGA testing and the 21-gene assay. Kim E. Economic analysis of decitabine versus best supportive care in the.…

  • Comparison of Estrogen and Progesterone Receptor Antibody.

    Jul 17, 2017. Early ER and PgR biochemical assays required fresh tumor. companies described in this article. For ER, the 3 antibody clones tested were 1D5, 6F11, and SP1; and. patient outcome correlated best with SP1 results.…

The Latest from ©