Anne Gangloff

Heterozygous familial hypercholesterolemia (HeFH) is a genetic disorder that accelerates atherosclerosis and leads to premature cardiovascular diseases (CVD). Whole food, plant-based diets (WFPB) are recommended worldwide for their cardioprotective properties but evidence regarding their effects in HeFH management remains unavailable. This study aims to evaluate the impact of a WFPB, in place of a standard American diet (SAD), on LDL-cholesterol (LDL-C) (primary outcome) and other CVD risk factors among adults with HeFH. In this randomized, two-period, two-treatment, crossover, controlled feeding trial, 50 adults with genetically confirmed HeFH, free of cholesterol-lowering medication, consumed a WFPB and a SAD for 4 weeks each in a random order, under fully controlled, isocaloric feeding conditions. The diets were separated by a two- to four-week washout period. LDL-C and other CVD risk factors were measured at the end of each diet. The WFPB induced a clinically significant reduction in LDL-C relative to the SAD ( − 17.9%, 95% CI: −21.7%, −14.3%; P < 0.0001). The study demonstrates the clinical significance of diet therapy in HeFH and supports its re-establishment as a cornerstone in clinical guidelines (clinicaltrials.gov registration: NCT05181553; funding: Canadian Institutes of Health Research).

Background/Objectives: Prostate cancer (PCa) cells are known to heavily depend on lipids to support their growth. We hypothesized that hyperlipidemic factors, for which inhibitors are already available and used to treat cardiovascular disease, would be dysregulated in metastatic PCa (mPCa). The goal of this case-control study, including 35 men per group, was to compare the levels of PCSK9, ANGPTL3, Apo CIII, leptin, and the lipid profile in patients with mPCa versus localized Gleason 8/9 PCa (lPCa) and patients at risk of developing PCa (controls). Methods: Protein levels were assessed using ELISAs, while lipids were measured using the Roche Cobas analytical platform. Results: The following circulating analytes were higher in mPCa: triglycerides (in mmol/L; controls 1.7 ± 1.2, lPCa 1.5 ± 0.7, mPCa 2.3 ± 1.2, p = 0.0004), Apo CIII (in µg/mL; control 110.7 ± 55.7, lPCa 115.0 ± 57.64, mPCa 159.9 ± 96.7, p = 0.0179), ANGPTL3 (in ng/mL; controls 41.7 ± 20.0, lPCa 42.8 ± 24.1, mPCa 57.3 ± 26.9, p = 0.0390), and leptin (in ng/mL, controls 9.6 ± 9.1, lPCa 8.2 ± 7.9, mPCa 17.7 ± 17.8, p < 0.0001). Surprisingly, PCSK9 levels were negatively correlated with LDL in the entire cohort. Conclusions: In this cohort of men, whole-body lipid metabolic rewiring is a feature restricted to the metastatic phase of prostate cancer, suggesting it may play a significant role in the progression toward more aggressive cancer forms. Given the availability of drugs targeting ANGPTL3 and Apo CIII, the therapeutic potential of these drugs should be evaluated in metastatic PCa.

INTRODUCTION: Metabolic disorders are risk factors for Alzheimer's disease (AD), although underlying mechanisms remain unclear. We investigated the relationship between peripheral metabolic markers – adiponectin, fibroblast growth factor 21 (FGF‐21), and insulin‐like growth factor binding protein 2 (IGFBP‐2) – and AD. METHODS: Participants with subjective cognitive decline (SCD), mild cognitive impairment (MCI), AD, and cognitively healthy (CH) controls were from the Consortium for the Early Identification of Alzheimer's Disease–Quebec cohort ( n = 287). Serum adiponectin, FGF‐21, and IGFBP‐2 concentrations were measured, compared between groups, and assessed for associations with clinical, cognitive, biochemical, and magnetic resonance imaging (MRI) data. RESULTS: Metabolic dysfunction was linked to lower adiponectin and IGFBP‐2, but higher FGF‐21. Both FGF‐21 and IGFBP‐2 increased with age and were inversely associated with cognitive performance. IGFBP‐2 was elevated at SCD stage and correlated with plasma tau phosphorylated at threonine 181 and amygdala atrophy. Adiponectin was unrelated to cognition. DISCUSSION: These findings suggest that IGFBP‐2 and, to a lesser extent, FGF‐21 may serve as early biomarkers of cognitive impairment, reflecting intricate links between peripheral dysmetabolism and AD.

STRUCTURED Introduction: Metabolic disorders are risk factors for Alzheimer’s disease (AD), although underlying mechanisms remain unclear. We investigated the relationship between peripheral metabolic markers – adiponectin, FGF-21 and IGFBP-2 – and AD. Methods: Participants with subjective cognitive decline (SCD), mild cognitive impairment (MCI), AD and cognitively healthy controls (CH) were from the CIMA-Q cohort (n=287). Serum adiponectin, FGF-21, and IGFBP-2 concentrations were measured, compared between groups, and assessed for associations with clinical, cognitive, biochemical and MRI data. Results: Metabolic dysfunction was linked to lower adiponectin and IGFBP-2, but higher FGF-21. Both FGF-21 and IGFBP-2 increased with age and were inversely associated with cognitive performance. IGFBP-2 was elevated at SCD stage and correlated with plasma pTau181 and amygdala atrophy. Adiponectin was unrelated to cognition. Discussion: These findings suggest that IGFBP-2, and FGF-21 to a lesser extent, may serve as early biomarkers of cognitive impairment, reflecting intricate links between peripheral dysmetabolism and AD.

Background: Some cancers have been found to require abundant supplies of lipids for their development. One example is prostate cancer (PCa). To date, lipid‐modifying factors, such as proprotein convertase subtilisin/kexin type 9 (PCSK9), angiopoietin‐like 3 protein (ANGPTL3), and lipoprotein(a) or Lp(a), have not been reported in men with PCa. The present study aimed to verify whether plasma levels of these lipid‐related proteins vary in men with PCa compared to at‐risk but cancer‐free men.Methods: Plasma samples from 35 men with locally advanced PCa Gleason 8 and 9 versus 35 men at risk of PCa were selected as cases and controls. Blood samples were paired according to age and BMI. Apolipoprotein B100 (Apo B), Lp(a), and lipid profiles were measured on an analytical platform (Roche Cobas). PCSK9 and ANGPTL3 levels were determined by ELISA.Results: No significant change in lipids and related factors levels was observed between men with localized PCa Gleason 8 or 9 and matched controls. A correlation between ANGPTL3 and HDL levels was only confirmed in controls (ρ = 0.54, p = 0.0009). PCSK9 was inversely associated with PSA levels in the entire cohort (ρ = −0.31, p < 0.01), suggesting that factors influencing PCSK9 could also influence PSA levels. In controls only, PSA levels were correlated with LDL, Apo B, non‐HDL, total cholesterol, and triglycerides (all ρ coefficients ≥ 0.35, all p‐values < 0.05). PCSK9 was correlated to LDL in PCa men, but the relationship was unexpectedly found to be inverse.Conclusions: In this observational study, lipid profiles, PCSK9, ANGPTL3, and Lp(a) levels did not change in men diagnosed with locally advanced Gleason 8 or 9 PCa compared to at‐risk but cancer‐free men. The present data suggest a complex interplay between PCSK9, PSA, and the lipid profile in localized PCa.

Pancreatic cancer is a complex malignancy associated with poor prognosis and high symptom burden. Optimal patient care relies on the integration of various sectors in the healthcare field as well as innovation through research. The Canadian National Pancreas Conference (NPC) was co-organized and hosted by Craig’s Cause Pancreatic Cancer Society and The Royal College of Physicians and Surgeons in November 2023 in Montreal, Canada. The conference sought to bridge the gap between Canadian healthcare providers and researchers who share the common goal of improving the prognosis, quality of life, and survival for patients with pancreatic cancer. The accredited event featured discussion topics including diagnosis and screening, value-based and palliative care, pancreatic enzyme replacement therapy, cancer-reducing treatment, and an overview of the current management landscape. The present article reviews the NPC sessions and discusses the presented content with respect to the current literature.

Cancer cells need constant supplies of lipids to survive and grow. Lipid dependence has been observed in various types of cancer, including high-grade serous ovarian carcinomas (HGSOC), which is a lethal form of gynecological malignancy. ANGPTL3, PCSK9, and Apo CIII are pivotal lipid-modulating factors, and therapeutic antibodies have been developed against each one (Evinacumab, Evolocumab and Volanesorsen, respectively). The roles -if any- of ANGPTL3, PCSK9, and Apo CIII in HGSOC are unclear. Moreover, levels of these lipid-modulating factors have never been reported before in HGSOC. In this study, circulating levels of ANGPTL3, PCSK9, and Apo CIII, along with lipid profiles, are examined to verify whether one or many of these lipid-regulating factors are associated with HGSOC. Methods ELISA kits were used to measure ANGPTL3, PCSK9 and Apo CIII levels in plasma samples from 31 women with HGSOC and 40 women with benign ovarian lesions (BOL) before treatment and surgery. A Roche Modular analytical platform measured lipid panels, Apo B and Lp(a) levels.Results ANGPTL3 levels were higher in women with HGSOC (84 ng/mL, SD: 29 ng/mL, n = 31) than in women with BOL (67 ng/mL, SD: 31 ng/mL, n = 40; HGSOC vs. BOL P = 0.019). Associations between the lipid panel and ANGPTL3, and the inverse relationship between HDL-cholesterol and triglycerides, were present in women with BOL but not with HGSOC. PCSK9 and Apo CIII were not associated with HGSOC.Conclusions In this cohort of 71 women, ANGPTL3 levels were increased in HGSOC patients. The presence of HGSOC disrupted the classic inverse relationship between HDL and triglycerides, as well as the association between the lipid panel and ANGPTL3. These associations were only maintained in cancer-free women. Given the availability of Evinacumab, a therapeutic antibody against ANGPTL3, the current finding prompts an assessment of whether ANGPTL3 inhibition has therapeutic potential in HGSOC.

Cholesterol plays an essential role in maintaining the rigidity of cell membranes and signal transduction. Various investigations confirmed empirically that the dysregulation of cholesterol homeostasis positively correlates with tumor progression. More specifically, recent studies suggested the distinct role of cholesterol in ovarian cancer cell proliferation, metastasis and chemoresistance. In this review, we summarize the current findings that suggest the contribution of cholesterol homeostasis dysregulation to ovarian cancer progression and resistance to anti-cancer agents. We also discuss the therapeutic implications of cholesterol-lowering drugs in ovarian cancer.

Background / synopsis: Cholesterol and lipids play an important role in sustaining tumor growth and metastasis in a large variety of cancers. ANGPTL3 and PCSK9 modify circulating cholesterol levels, thus availability of lipids to peripheral cells. Little is known on the role, if any, of circulating lipid-related factors such as PCSK9, ANGPTL3 and lipoprotein (a) in cancers. Objective/purpose: To compare circulating levels of PCSK9, ANGPTL3, and Lp(a) in women with stage III breast cancer versus women with premalignant or benign breast lesions. Methods: Twenty-three plasma samples from women diagnosed with a stage III breast cancer (ductal, lobular or mixed) were matched for age with twenty-three plasma samples from women bearing premalignant (stage 0, n = 9) or benign (n = 14) breast lesions. The lipid profile (Apo B, total cholesterol, HDL cholesterol and triglycerides levels) and Lp(a) were measured on a Roche Modular analytical platform, whereas LDL levels were calculated with the Friedewald formula. ANGPTL3 and PCSK9 plasma levels were quantitated by ELISA. All statistical analyses were performed using SAS software version 9.4. Results: PCSK9 levels were significantly higher in women with stage III breast cancer compared to age-matched counterparts presenting a benign lesion (95.9 ± 27.1 ng/mL vs. 78.5 ± 19.3 ng/mL, p < 0.05, n = 14). Moreover, PCSK9 levels positively correlated with breast disease severity (benign, stage 0, stage III) (Rho = 0.34, p < 0.05, n = 46). In contrast, ANGPTL3 and Lp(a) plasma levels did not display any association with breast disease status and lipids did not correlate with disease severity. Conclusion: In this small cohort of 46 women, PCSK9 levels tended to increase with the severity of the breast disease. Given that PCSK9 plays an important role in maintaining cholesterolemia, and a potential role in tumor evasion, present results warrant further investigation into a possible association between PCSK9 levels and breast cancer severity in larger cohorts of women.