69 research outputs found
Higher overall survival in metastatic pancreatic cancer: the impact of where and how treatment is delivered
HER2 therapy: Molecular mechanisms of trastuzumab resistance
Trastuzumab is a monoclonal antibody targeted against the HER2 tyrosine kinase receptor. The majority of patients with metastatic breast cancer who initially respond to trastuzumab develop resistance within one year of treatment initiation, and in the adjuvant setting 15% of patients still relapse despite trastuzumab-based therapy. In this review, we discuss potential mechanisms of antitumor activity by trastuzumab, and how these mechanisms become altered to promote therapeutic resistance. We also discuss novel therapies that may improve the efficacy of trastuzumab, and that offer hope that the survival of breast cancer patients with HER2-overexpressing tumors can be vastly improved
LSD but not lisuride disrupts prepulse inhibition in rats by activating the 5-HT2A receptor
Compounds that activate the 5-HT2A receptor, such as lysergic acid diethylamide (LSD), act as hallucinogens in humans. One notable exception is the LSD congener lisuride, which does not have hallucinogenic effects in humans even though it is a potent 5-HT2A agonist. LSD and other hallucinogens have been shown to disrupt prepulse inhibition (PPI), an operational measure of sensorimotor gating, by activating 5-HT2A receptors in rats.
We tested whether lisuride disrupts PPI in male SpragueβDawley rats. Experiments were also conducted to identify the mechanism(s) responsible for the effect of lisuride on PPI and to compare the effects of lisuride to those of LSD.
Confirming a previous report, LSD (0.05, 0.1, and 0.2Β mg/kg, s.c.) reduced PPI, and the effect of LSD was blocked by pretreatment with the selective 5-HT2A antagonist MDL 11,939. Administration of lisuride (0.0375, 0.075, and 0.15Β mg/kg, s.c.) also reduced PPI. However, the PPI disruption induced by lisuride (0.075Β mg/kg) was not blocked by pretreatment with MDL 11,939 or the selective 5-HT1A antagonist WAY-100635 but was prevented by pretreatment with the selective dopamine D2/D3 receptor antagonist raclopride (0.1Β mg/kg, s.c).
The effect of LSD on PPI is mediated by the 5-HT2A receptor, whereas activation of the 5-HT2A receptor does not appear to contribute to the effect of lisuride on PPI. These findings demonstrate that lisuride and LSD disrupt PPI via distinct receptor mechanisms and provide additional support for the classification of lisuride as a non-hallucinogenic 5-HT2A agonist
Mammalian sex determinationβinsights from humans and mice
Disorders of sex development (DSD) are congenital conditions in which the development of chromosomal, gonadal, or anatomical sex is atypical. Many of the genes required for gonad development have been identified by analysis of DSD patients. However, the use of knockout and transgenic mouse strains have contributed enormously to the study of gonad gene function and interactions within the development network. Although the genetic basis of mammalian sex determination and differentiation has advanced considerably in recent years, a majority of 46,XY gonadal dysgenesis patients still cannot be provided with an accurate diagnosis. Some of these unexplained DSD cases may be due to mutations in novel DSD genes or genomic rearrangements affecting regulatory regions that lead to atypical gene expression. Here, we review our current knowledge of mammalian sex determination drawing on insights from human DSD patients and mouse models
Biomechanical analysis of penile erections: penile buckling behaviour under axial loading and radial compression
Police Officersβ and Paramedicsβ Experiences with Overdose and Their Knowledge and Opinions of Washington Stateβs Drug OverdoseβNaloxoneβGood Samaritan Law
The out-of-region bias: Distance estimations based on geographic category membership
Distance estimates, Geographic reasoning, Spatial categorization, Conceptual bias, Store choice,
Anti-tumor effect of the insulin-like growth factor-1 receptor (IGF-1R) on human pancreatic cancer cells in both in vitro and in vivo studies
- β¦