Comparison of the PharmDx immunohistochemical system with standard methods for assessing estrogen and progesterone receptors in invasive carcinoma of the breast.

Aim: Accurate assessment of estrogen receptor (ER) and progesterone receptor (PR) status of breast cancers is essential for selecting patients for endocrine treatment. This study aimed to compare immunohistochemistry for these markers using the pharmDx system and standard methods.

Methods: Sections of 203 core biopsies of invasive carcinoma of the breast were stained for ER and PR using the pharmDx system and standard methods.

Efficacy of caspofungin in a juvenile mouse model of central nervous system candidiasis.

Neonatal candidiasis is an increasingly common occurrence causing significant morbidity and mortality and a higher risk of dissemination to the central nervous system (CNS) than that seen with older patients. The current understanding of optimal antifungal therapy in this setting is limited. We have developed a model of disseminated candidiasis with CNS involvement in juvenile mice to assess the efficacy of the echinocandin caspofungin relative to amphotericin B (AmB).

Impaired S-phase arrest in acute myeloid leukemia cells with a FLT3 internal tandem duplication treated with clofarabine.

Purpose: Acute myeloid leukemia cells with an internal tandem duplication mutation of FLT3 (FLT3-ITD) have effective DNA repair mechanisms on exposure to drugs. Despite this, the phenotype is not associated with primary resistant disease. We show defects in the response of mutant FLT3 AML cells to the S-phase drug clofarabine that could account for the apparent contradiction.

The reliability of assessment of oestrogen receptor expression on needle core biopsy specimens of invasive carcinomas of the breast.

Aim: To assess the reliability of assessment of oestrogen receptor expression on needle core biopsy specimens of invasive carcinomas of the breast. Previous studies have mostly been small, with a range of agreement from 62% to 100%.

Methods: Retrospective audit of 338 tumours surgically excised within 60 days of core biopsy, that had had oestrogen receptor assessed on both the core biopsy and tumour specimens.

Prevention of obesity in mice by antisense oligonucleotide inhibitors of stearoyl-CoA desaturase-1.

Effective therapies for the treatment of obesity, a key element of metabolic syndrome, are urgently needed but currently lacking. Stearoyl-CoA desaturase-1 (SCD1) is the rate-limiting enzyme catalyzing the conversion of saturated long-chain fatty acids into monounsaturated fatty acids, which are major components of triglycerides. In the current study, we tested the efficacy of pharmacological inhibition of SCD1 in controlling lipogenesis and body weight in mice.

Do poor-prognosis breast tumours express membrane cofactor proteins (CD46)?

Unlabelled: CD46 or membrane cofactor protein (MCP) is a complement regulatory protein that has been identified on all nucleated cells and which protects them from attack by autologous complement. Breast carcinomas are reported to consistently express CD46.

Aim And Methods: Our previous immunohistochemical study showed that in breast carcinomas, loss of CD59 and CD55 correlated with poor survival.

Mice lacking dipeptidyl peptidase IV are protected against obesity and insulin resistance.

Dipeptidyl peptidase IV (DP-IV), a member of the prolyl oligopeptidase family of peptidases, is involved in the metabolic inactivation of a glucose-dependent insulinotropic hormone, glucagon-like peptide 1 (GLP-1), and other incretin hormones. Here, we investigated the impact of DP-IV deficiency on body weight control and insulin sensitivity in mice. Whereas WT mice displayed accelerated weight gain and hyperinsulinemia when fed a high-fat diet (HFD), mice lacking the gene encoding DP-IV (DP-IV-/-) are refractory to the development of obesity and hyperinsulinemia.