Efficacy in diet-induced obese mice of the hepatotropic, peripheral cannabinoid 1 receptor inverse agonist TM38837.

Background And Purpose: The cannabinoid CB receptor has a well-established role in appetite regulation. Drugs antagonizing central CB receptors, most notably rimonabant, induced weight loss and improved the metabolic profile in obese individuals but were discontinued due to psychiatric side effects. However, metabolic benefits were only partially attributable to weight loss, implying a role for peripheral receptors, and peripherally restricted CB receptor antagonists have since been of interest.

Optimizing and characterizing 4-methyl substituted pyrazol-3-carboxamides leading to the peripheral cannabinoid 1 receptor inverse agonist TM38837.

Several series of diverse pyrazole-3-carboxamides functionalized with 4-methylamides, 4-methylcarboxylic acids and 4-methyltetrazoles were prepared from the corresponding 4-cyanomethylpyrazoles and investigated as Cannabinoid receptor 1 (CB1) antagonists and inverse agonists with the aim of making compounds with less CNS (Central Nervous System) mediated side-effects compared to rimonabant. The compounds were evaluated and optimized with respect to lipophilicity, solubility, CB1 potency, metabolism, distribution to brain and liver, effect on weight loss in diet-induced mice models. A few carboxylic acids and tetrazoles were selected as especially promising with the tetrazole TM38837 subsequently demonstrating impressive efficacy in various animal models of obesity, producing considerable weight loss and improvements on plasma markers of inflammation and glucose homeostasis, at doses apparently producing negligible brain exposure.

Increased incidence and improved survival in endometrial cancer in Sweden 1960-2014: a population-based registry survey.

Background: An investigation of trends of incidence and net survival (NS) for endometrial cancer in Sweden.

Methods: Morphologically verified endometrial carcinoma diagnosed 1960 to 2014 were collected from the nation-wide Swedish Cancer Registry. Endometrial cancer patients were assessed with regards to time trends for incidence and 54,825 cases remained for survival analyses.

An overview of Clinical Quality Registries (CQRs) on gynecological oncology worldwide.

Introduction: Clinical Quality Registries (CQRs) were initiated in order to compare clinical outcomes between hospitals or regions within a country. To get an overview of these CQRs worldwide the aim of this study was to identify these CQRs for gynecological oncology and to summarize their characteristics, processes and QI's and to establish whether it is feasible to make an international comparison in the future.

Methods: To identify CQRs in gynecological oncology a literature search in Pubmed was performed.

Time Trends for Incidence and Net Survival of Cervical Cancer in Sweden 1960-2014-A Nationwide Population-Based Study.

Background: The aim was to investigate time trends for incidence and long-term net survival in the morphologic subtypes and stages of cervical cancer in Sweden during the period 1960 to 2014.

Methods: Women with invasive cervical cancer were identified through the Swedish Cancer Registry. Incidence and net survival were calculated according to morphology, age at diagnosis, and FIGO stage at diagnosis.