Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.108 (TAT)
 2,389 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antitumor activity of a newly synthesized triphenylethylene derivative [(E)-4-[1-[4-[2-(dimethylamino)ethoxy-phenyl]-2-(4-isopropyl)phenyl-1- butenyl] phenyl monophosphate] (TAT-59) was investigated against human breast carcinoma xenografts in nude mice with reference to the changes of hormone receptors. Five strains (MCF-7, Br-10, R-27, ZR-75-1, and T-61) used for the experiments possessed cytosol estrogen receptor (ER), and their growth was estradiol dependent. Five mg of TAT-59 and tamoxifen citrate (TAM) per kg were administered p.o. daily except Sunday. TAT-59 showed a positive antitumor effect against MCF-7 and R-27, whereas TAM was effective on MCF-7, and their adverse effects detected by mortality rate, body weight loss, and spleen weight loss were similar to each other. The reduction of ER and production of progesterone receptor (PgR) after the treatment with TAT-59 were more potent than after TAM, suggesting that TAT-59 exerts its antitumor effect through binding to ER. These findings suggest that TAT-59 might merit use in clinical trials with breast cancers.
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PMID:Antitumor effect of triphenylethylene derivative (TAT-59) against human breast carcinoma xenografts in nude mice. 143 57

TAT-59 ((E)-4-[1-[4-[2-(dimethylamino)ethoxy]-phenyl]-2-(4- isopropyl)phenyl-1-butenyl]-phenyl-monophosphate) treatment was performed on hormone-dependent MCF-7 tumors in athymic mice. TAT-59 given at 1, 5, and 20 mg/kg inhibited the estrogen-stimulated growth of MCF-7 tumors in athymic mice in a dose-dependent fashion. The most clear decrease in tumor growth was shown in the TAT-59 alone group, although it was not dramatic. Average serum concentrations of DP-TAT-59((Z)-[1-[4-[2-(dimethylamino)- ethoxy]phenyl]-2-(4-isopropyl)phenyl-1-butenyl]-4-hydroxybenzene) and DM-DP-TAT-59(desmethyl-DP-TAT-59), metabolites of TAT-59, increased in a dose-dependent manner. Much higher levels of DP-TAT-59 and DM-DP-TAT-59 were shown in tumors (target tissues of estrogen) as compared with muscles (nontarget tissues of estrogen) or serum. A serum concentration of DP-TAT-59 or DM-DP-TAT-59 corresponding to the physiologic levels of serum estradiol in premenopausal women was sufficient to inhibit the estrogen-stimulated growth of MCF-7 tumors in mice. TAT-59 induced a dose-dependent increase in estrogen receptor levels in the MCF-7 tumors. In contrast, it prevented the estradiol (E2)-induced increase in progesterone receptor levels in a dose-dependent manner. Insulin-like growth factor 1 levels measured in the MCF-7 tumors significantly decreased in the TAT-59 alone group and in the no treatment group as compared with the E2 alone group. These results show the pronounced antiestrogenic action of TAT-59 on hormone-dependent MCF-7 tumors in athymic mice.
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PMID:A new triphenylethylene derivative, TAT-59; hormone receptors; insulin-like growth factor 1; and growth suppression of hormone-dependent MCF-7 tumors in athymic mice. 807 3

Triple negative breast cancers are an aggressive subtype of breast cancer, characterized by the lack of estrogen receptor, progesterone receptor and Her2 expression. Triple negative breast cancers are non-responsive to conventional anti-hormonal and Her2 targeted therapies, making it necessary to identify new molecular targets for therapy. The chemokine CCL2 is overexpressed in invasive breast cancers, and regulates breast cancer progression through multiple mechanisms. With few approaches to target CCL2 activity, its value as a therapeutic target is unclear. In these studies, we developed a novel gene silencing approach that involves complexing siRNAs to TAT cell penetrating peptides (Ca-TAT) through non-covalent calcium cross-linking. Ca-TAT/siRNA complexes penetrated 3D collagen cultures of breast cancer cells and inhibited CCL2 expression more effectively than conventional antibody neutralization. Ca-TAT/siRNA complexes targeting CCL2 were delivered to mice bearing MDA-MB-231 breast tumor xenografts. In vivo CCL2 gene silencing inhibited primary tumor growth and metastasis, associated with a reduction in cancer stem cell renewal and recruitment of M2 macrophages. These studies are the first to demonstrate that targeting CCL2 expression in vivo may be a viable therapeutic approach to treating triple negative breast cancer.
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PMID:Targeted gene silencing of CCL2 inhibits triple negative breast cancer progression by blocking cancer stem cell renewal and M2 macrophage recruitment. 2728 85

The purpose of this study was to evaluate the prognostic significance of computed tomography (CT)-attenuation of tumor-adjacent breast adipose tissue for predicting recurrence-free survival (RFS) in patients with breast cancer. We retrospectively enrolled 287 breast cancer patients who underwent pretreatment 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT. From non-contrast-enhanced CT images of PET/CT, CT-attenuation values of tumor-adjacent breast adipose tissue (TAT HU) and contralateral breast adipose tissue (CAT HU) were measured. Difference (HU difference) and percent difference (HU difference %) in CT-attenuation values between TAT HU and CAT HU were calculated. The relationships of these breast adipose tissue parameters with tumor factors and RFS were assessed. TAT HU was significantly higher than CAT HU (p < 0.001). TAT HU, HU difference, and HU difference % showed significant correlations with T stage and estrogen receptor and progesterone receptor status (p < 0.05), whereas CAT HU had no significant relationships with tumor factors (p > 0.05). Patients with high TAT HU, HU difference, and HU difference % had significantly worse RFS than those with low values (p < 0.001). In multivariate analysis, TAT HU and HU difference % were significantly associated with RFS after adjusting for clinico-pathologic factors (p < 0.05). CT-attenuation of tumor-adjacent breast adipose tissue was significantly associated with RFS in patients with breast cancer. The findings seem to support the close contact between breast cancer cells and tumor-adjacent adipocytes observed with imaging studies.
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PMID:Prognostic Significance of CT-Attenuation of Tumor-Adjacent Breast Adipose Tissue in Breast Cancer Patients with Surgical Resection. 3139 63