- Large-scale detection of drug off-targets: hypotheses for drug repurposing and understanding side-effects. [Journal Article]
- BPBMC Pharmacol Toxicol 2017 Apr 28; 18(1):18
- CONCLUSIONS: The detection of molecular interaction field similarities provide the opportunity to suggest drug repurposing opportunities as well as to identify potential molecular mechanisms responsible for side-effects. All methods utilized are freely available and can be readily applied to new query binding-sites. All data is freely available and represents an invaluable source to identify further candidates for repurposing and suggest potential mechanisms responsible for side-effects.
- [Calcium and bone metabolism across women's life stages. Bone quality and treatment of osteoporosis by SERM.] [Journal Article]
- CCClin Calcium 2017; 27(5):723-732
- Estrogen deficiency induces bone resorption and bone collagen crosslink abnormalities such as reductions in enzymatic cross-links and accumulation of Advanced glycation end products(AGEs). In this re...
Estrogen deficiency induces bone resorption and bone collagen crosslink abnormalities such as reductions in enzymatic cross-links and accumulation of Advanced glycation end products(AGEs). In this review, we described that the mechanism of poor bone quality in estrogen deficiency and how selective estrogen receptor modulators such as raloxifene and bazedoxifene improve bone structural and material properties.
- Growth-suppressive activity of raloxifene on liver cancer cells by targeting IL-6/GP130 signaling. [Journal Article]
- OOncotarget 2017 Apr 06
- CONCLUSIONS: Our results suggest that Raloxifene is a potent IL-6/GP130 inhibitor and may be a chemoprevention agent for liver cancer by targeting persistent STAT3 signaling.
- A peek into the drug development scenario of endometriosis - A systematic review. [Review]
- BPBiomed Pharmacother 2017 Apr 10; 90:575-585
- CONCLUSIONS: From the literature review, it appears that the most promising molecules for the treatment of endometriosis in the near future include elagolix, mifepristone, TAK-385, KLH-2109 and ASP1707 and cabergoline. It remains to be seen if these molecules would succeed large phase 3 clinical trials and overcome the regulatory hurdles to become an essential tool in the gynaecologist's armamentarium against endometriosis.
- A Novel Strategy to Co-target Estrogen Receptor and Nuclear Factor κB Pathways with Hybrid Drugs for Breast Cancer Therapy. [Journal Article]
- HCHorm Cancer 2017 Apr 10
- Nearly 75% of breast tumors express estrogen receptor (ER), and will be treated with endocrine therapy, such as selective estrogen receptor modulator (SERM), tamoxifen, or aromatase inhibitors. Despi...
Nearly 75% of breast tumors express estrogen receptor (ER), and will be treated with endocrine therapy, such as selective estrogen receptor modulator (SERM), tamoxifen, or aromatase inhibitors. Despite their proven success, as many as 40-50% of ER+ tumors fail to respond to endocrine therapy and eventually recur as aggressive, metastatic cancers. Therefore, preventing and/or overcoming endocrine resistance in ER+ tumors remains a major clinical challenge. Deregulation or activation of the nuclear factor κB (NFκB) pathway has been implicated in endocrine resistance and poor patient outcome in ER+ tumors. As a consequence, one option to improve on existing anti-cancer treatment regimens may be to introduce additional anti-NFκB activity to endocrine therapy drugs. Our approach was to design and test SERM-fumarate co-targeting hybrid drugs capable of simultaneously inhibiting both ER, via the SERM, raloxifene, and the NFκB pathway, via fumarate, in breast cancer cells. We find that the hybrid drugs display improved anti-NFκB pathway inhibition compared to either raloxifene or fumarate. Despite some loss in potency against the ER pathway, these hybrid drugs maintain anti-proliferative activity in ER+ breast cancer cells. Furthermore, these drugs prevent clonogenic growth and mammosphere formation of ER+ breast cancer cells. As a proof-of-principle, the simultaneous inhibition of ER and NFκB via a single bifunctional hybrid drug may represent a viable approach to improve the anti-inflammatory activity and prevent therapy resistance of ER-targeted anti-cancer drugs.
- Benefits and Harms of Osteoporosis Medications in Patients With Chronic Kidney Disease: A Systematic Review and Meta-analysis. [Journal Article]
- AIMAnn Intern Med 2017 Apr 11
- CONCLUSIONS: Effects of osteoporosis medications on BMD, fracture risk, and safety among patients with CKD are not clearly established.
- Raloxifene but not alendronate can compensate the impaired osseointegration in osteoporotic rats. [Journal Article]
- COClin Oral Investig 2017 Mar 29
- CONCLUSIONS: These findings suggest that raloxifene but not alendronate can compensate for the impaired osseointegration in osteoporotic rats.Regarding the superiority of raloxifene observed in the improvement of bone dynamics response, this statement suggests that raloxifene could be a good option for osteoporosis patients in oral rehabilitation procedures.
- Melasma treatment: A novel approach using a topical agent that contains an anti-estrogen and a vascular endothelial growth factor inhibitor. [Journal Article]
- MHMed Hypotheses 2017; 101:1-5
- Melasma is an acquired disorder of pigmentation that presents with asymptomatic symmetric darkening of the face. The pathogenesis of this condition is multifactorial and influenced by several factors...
Melasma is an acquired disorder of pigmentation that presents with asymptomatic symmetric darkening of the face. The pathogenesis of this condition is multifactorial and influenced by several factors including female sex hormones, genetic predisposition and ultraviolet light exposure. The management of melasma is usually directed at more than one of the causative etiologic factors and often incorporates a combination of topical agents, with or without the addition of physical modalities. Estrogen and angiogenesis are significant factors in the etiology of melasma. A useful addition to the therapeutic armentarium for treating melasma would include a topical agent that could effect both of these causative factors. Specifically, a topical preparation consisting of an anti-estrogen and a vascular endothelial growth factor inhibitor would accomplish this goal. Suitable candidates that target estrogen receptors and vascular endothelial growth factor are currently used in medical oncology as systemic antineoplastic agents. The anti-estrogen could be either a selective estrogen receptor modulator (such as tamoxifen or raloxifene) or an aromatase inhibitor (such as anastrozole or letrozole or exemestane). The vascular endothelial growth factor inhibitor would be bevacizumab. In conclusion, a novel-topically administered-therapy for melasma would combine an anti-estrogen and a vascular endothelial growth factor inhibitor.
- Involvement of HSP70 and HO-1 in the protective effects of raloxifene on multiple organ dysfunction syndrome by endotoxemia in ovariectomized rats. [Journal Article]
- MMenopause 2017 Mar 27
- CONCLUSIONS: Long-term treatment with raloxifene reduces the severity of sepsis in OVX rats, attributed from up-regulation of HSP70 and HO-1 to exert the antioxidant and anti-inflammatory capacities. These findings provide new insights into bacterial infection during menopause and the molecular mechanism of raloxifene.
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- Simultaneous LC-MS-MS Determination of Lopinavir and Rifabutin in Human Plasma. [Journal Article]
- JCJ Chromatogr Sci 2017 Mar 03; :1-8
- Tuberculosis (TB) with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome represents the most common infectious diseases worldwide. Anti-TB drugs are used concurrently with antiret...
Tuberculosis (TB) with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome represents the most common infectious diseases worldwide. Anti-TB drugs are used concurrently with antiretroviral drug for treatment of TB-HIV co-morbidities. Due to lower risk of interaction with protease inhibitors, rifabutin is preferred over rifampicin in treatment of HIV and TB co-morbidity. A simple and specific liquid chromatography tandem mass spectrometry method was developed for quantification of rifabutin (RBT) and lopinavir (LPV) simultaneously in human plasma. Following extraction using 60% n-hexane in ethyl acetate, the processed samples were chromatographed on a Discovery HS C18 column (5 μm, 50 × 4.6 mm, id) using mobile phase [85% acetonitrile in ammonium acetate buffer (10 mM, pH 4.5)] at a flow rate of 0.7 mL/min. Mass spectrometric detection was performed in positive electrospray ionization mode using multiple reaction monitoring (RBT, m/z 847.7 → 815.4; LPV, m/z 629.6 → 447.4). Raloxifene and phenacetin were used as internal standards for RBT and LPV, respectively. Linearity was established in the range of 1-1,000 ng/mL and 0.5-10 µg/mL (R2 ≥ 0.99) for RBT and LPV, respectively. The recovery of LPV and RBT were always >90 and >50%, respectively. The precisions and accuracies were well within the acceptable limits of variation.