👤 Annick Vachon

In a previous study, we showed that oral supplementation with lysophosphatidylcholine (LPC)-bound omega-3 fatty acids (n-3) increases cortical eicosapentaenoic acid (EPA, C20:5n-3) but not docosahexaenoic acid (DHA, C22:6n-3) in an apolipoprotein E (APOE)- and duration-dependent manner. This may reflect DHA retention in blood-brain interfaces, such as microvessels (MV) and choroid plexus (ChP). To assess whether LPC n-3 intake over two or four months modulates the lipid composition of MV and ChP in APOE3 and APOE4 mice. APOE3 and APOE4 mice received daily gavage of LPC-bound EPA (21.5 mg/day) and DHA (10.4 mg/day) or sunflower oil (control) for two or four months (n=5-8 mice per genotype and treatment). Lipids from plasma, frontal cortex (FCx), ChP, and MV were analyzed by liquid chromatography-tandem mass spectrometry. Principal component analysis indicated that phospholipid levels in plasma, ChP, MV and FCx were modulated more by the type of oil administered by gavage (LPC n-3-enriched oil vs. sunflower oil) than by APOE genotype or gavage duration. The ChP was the most responsive tissue to n-3 supplementation. Total DHA increased in the FCx of APOE3 mice receiving LPC n-3, but not in APOE4 mice. In contrast, EPA levels were significantly higher across genotypes and biological compartments in n-3-supplemented mice. This study reports higher DHA and EPA concentrations in the brain of APOE3 mice supplemented with LPC n‑3 and reinforces evidence of lower DHA accretion in APOE4 mice. It also identifies the ChP as a major site of n‑3 response. Show less

Pyoderma gangrenosum (PG) is a rare, noninfectious, truly nongangrenous, autoinflammatory condition marked by neutrophilic dermatosis. It is characterized by the rapid onset of painful, full-thickness, ulcerative skin lesions with distinctive violaceous and undermined borders. PG is commonly associated with autoimmune and hematologic disorders, namely, inflammatory bowel disease (IBD) and monoclonal gammopathy of undetermined significance (MGUS). However, it has less commonly been reported in association with lymphoplasmacytic lymphoma (LPL) and rarely with its subtype, Waldenström macroglobulinemia (WM). This case unfolds the story of a 72-year-old female patient with a complex medical and primarily cutaneous oncological history, who initially developed painful lesions on her shins suspected to be PG with a superimposed infection. During extensive infectious, rheumatologic, and oncologic workup revealing an IgM monoclonal gammopathy and antibiotic-resistant infections, her condition quickly deteriorated with altered mental status and eventual cardiopulmonary arrest 2 months after the initial PG diagnosis. This case highlights the importance of close follow-up after PG identification for unusual underlying malignancies and suggests that even an indolent malignancy like WM can contribute to aggressive clinical decline in this setting. Show less

Aberrant Wnt/beta-catenin signaling leading to nuclear accumulation of the oncogene product beta-catenin is observed in a wide spectrum of human malignancies. The destruction complex in the Wnt/beta-catenin pathway is critical for regulating the level of beta-catenin in the cytoplasm and in the nucleus. Here, we report a comprehensive study of the contribution of genetic variation in six genes encoding the beta-catenin destruction complex (APC, AXIN1, AXIN2, CSNK1D, CSNK1E, and GSK3B) to breast cancer using a Mayo Clinic Breast Cancer Case-Control Study. A total of 79 candidate functional and tagging single nucleotide polymorphisms (SNP) were genotyped in 798 invasive cases and 843 unaffected controls. Of these, rs454886 in the APC tumor suppressor gene was associated with increased breast cancer risk (per allele odds ratio, 1.23; 95% confidence intervals, 1.05-1.43; P(trend) = 0.01). In addition, five SNPs in AXIN2 were associated with increased risk of breast cancer (P(trend) < 0.05). Haplotype-based tests identified significant associations between specific haplotypes in APC and AXIN2 (P < or = 0.03) and breast cancer risk. Further characterization of the APC and AXIN2 variants suggested that AXIN2 rs4791171 was significantly associated with risk in premenopausal (P(trend) = 0.0002) but not in postmenopausal women. The combination of our findings and numerous genetic and functional studies showing that APC and AXIN2 perform crucial tumor suppressor functions suggest that further investigation of the contribution of AXIN2 and APC SNPs to breast cancer risk are needed. Show less