Towards Multitargeted Ligands as Pain Therapeutics: Dual Ligands of the Caα2δ-1 Subunit of Voltage-Gated Calcium Channel and the μ-Opioid Receptor.

The synthesis and pharmacological activity of a new series of dual ligands combining activities towards the α2δ-1 subunit of voltage-gated calcium channels (Caα2δ-1) and the μ-opioid receptor (MOR) as novel pain therapeutics are reported. A careful exploration of the pharmacophores related to both targets, which in principle had few common characteristics, led to the design of novel compounds exhibiting both activities. The construction of the dual ligands started from published Caα2δ-1 ligands, onto which MOR ligand pharmacophoric elements were added.

Estrogen Receptor Alpha Gene Amplification Is an Independent Predictor of Long-Term Outcome in Postmenopausal Patients with Endocrine-Responsive Early Breast Cancer.

Purpose: Estrogen receptor (ER) expression is a prognostic parameter in breast cancer, and a prerequisite for the use of endocrine therapy. In ER+ early breast cancer, however, no receptor-associated biomarker exists that identifies patients with a particularly favorable outcome. We have investigated the value of ESR1 amplification in predicting the long-term clinical outcome in tamoxifen-treated postmenopausal women with endocrine-responsive breast cancer.

The Value of Detecting Pathological Changes During Clot Formation in Early Disease Treatment-Naïve Breast Cancer Patients.

Breast cancer (BC) is one of the most prevalent forms of cancer in women worldwide. Clinical research indicates that BC patients are at an increased risk for thrombotic events, drastically decreasing their quality-of-life and treatment outcomes. There is ample evidence of this in the literature, but it is mainly focused on metastatic BC.

Amplification Associates with Aggressive Phenotype but Not Markers of AKT-MTOR Signaling in Endometrial Carcinoma.

Purpose: Amplification of , encoding the PI3K catalytic subunit alpha, is common in uterine corpus endometrial carcinoma (UCEC) and linked to an aggressive phenotype. However, it is unclear whether amplification acts via PI3K activation. We investigated the association between amplification, markers of PI3K activity, and prognosis in a large cohort of UCEC specimens.

[Emergency Medicine in Remote Settings].

For many acute diseases and injuries, treatment does not differ between industrialised environment and wilderness setting. However, for some emergencies, treatment needs to be adapted if advanced medical care facilities cannot be reached within 4 hours.In these situations, dislocated joints and fractures should be reduced quickly.