scholarly journals Associations of Long Chain Polyunsaturated Fatty Acid Biomarkers with Affective Symptoms and Cognition in Women Beginning Chemotherapy for Breast Cancer

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 366-366
Author(s):  
Zihan Zhang ◽  
Kate Ormiston ◽  
Tonya Orchard ◽  
Maryam Lustberg ◽  
Patrick Schnell
Keyword(s):  
Breast Cancer ◽  
Fatty Acids ◽  
Executive Function ◽  
Comprehensive Cancer Center ◽  
Chain Polyunsaturated Fatty Acid ◽  
Cancer Center ◽  
Total N ◽  
Loneliness Scale ◽  
Affective Symptoms ◽  
Long Chain

Abstract Objectives The objective of this research was to examine if the serum levels of long chain omega 3 fatty acids (LCn-3 FA) or long chain omega-6 fatty acids (LCn-6 FA) were associated with affective symptoms and cognition in breast cancer patients beginning chemotherapy. Methods 60 women with breast cancer were assigned to a double-blinded randomized study of minocycline vs placebo. Serum was collected from 53 women at baseline and post-chemotherapy and was stored at −80C. Serum fatty acids (FAs) from 37 pairs of samples from both time points were extracted, methylated, then analyzed using gas chromatography. Changes in fatty acids were analyzed by using paired sample t-test. Cognitive and affective behaviors were measured by Behavior Rating Inventory of Executive Function—Adult Version (BRIEF-A) test, The State-Trait Anxiety Inventory (STAI), and UCLA 3 item Loneliness Scale. Associations between baseline FAs and cognitive and affective test scores were measured by Pearson correlations; p < 0.05 was considered significant. Results Preliminary results suggest there were significant increases in the following serum FAs from baseline to post chemotherapy: C14:0 (p < 0.05) and C18:1n9 (p < 0.05), and there were significant decreases in C18:0 (p = 0.01), C20:0 (p = 0.001), and C22:5n6 (p < 0.05). Baseline analysis, prior to chemotherapy, indicated a non-significant trend for EPA (20:5n3) (r = −0.27, p = 0.06) and the n-3/n-6 ratio (r = −0.27, p = 0.06) to be correlated with better (i.e., lower) scores on the BRIEF-A test. There were trends for correlations of total n-6 FA and better (i.e., lower) STAI score (r = −0.25, p = 0.07), and total n-6 FA and better (i.e., lower) Loneliness Scale scores (r = −0.24, p = 0.09). Conclusions There was a significant change in the serum FA profile of women with breast cancer from baseline to post-chemotherapy. There were non-significant trends for n-3 FAs to be associated with better executive function, and n-6 FAs to be correlated with less anxiety and loneliness prior to beginning chemotherapy. Future research will investigate associations among serum FAs, cognitive and affective tests post-chemotherapy. Funding Sources Stephanie Spielman Breast Cancer Center – Kroger Fund OSU Comprehensive Cancer Center Pelotonia Award.

scholarly journals Changes in Serum Fatty Acids and Inflammatory Markers in Postmenopausal Women With Breast Cancer Following Chemotherapy Treatment

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 290-290
Author(s):  
Zihan Zhang ◽  
Kate Ormiston ◽  
Patrick Schnell ◽  
Rachel Kopec ◽  
Maryam Lustberg ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Fatty Acids ◽  
Inflammatory Markers ◽  
Postmenopausal Breast Cancer ◽  
Cancer Center ◽  
Future Research ◽  
Total N ◽  
Serum Cytokines ◽  
Significant Difference ◽  
Serum Fatty Acids

Abstract Objectives Chemotherapy induces an inflammatory state. Fatty acids (FAs) are potent signaling molecules that can alter inflammation. The objective of this research was to examine if serum fatty acids and inflammatory markers in postmenopausal breast cancer patients changed during and after chemotherapy. Methods Serum samples from 60 women undergoing chemotherapy for breast cancer were collected at baseline (n = 50), the fourth cycle of chemotherapy (chemo-4; n = 40), and 6 months after chemotherapy (6M post-chemo; n = 34). Serum F As were extracted, methylated, then analyzed using gas chromatography; serum cytokines were analyzed using multiplex enzyme-linked immunoassay. After natural log-transformation data were analyzed by one-way analysis of variance (ANOVA) followed by post hoc tests using Tukey's Honest Significant Difference test. Results From baseline to chemo-4, C18:0, C20:0, and C22:5n6 significantly decreased (P < 0.05 for all) while C18:1n9, total n-9 FAs, total monounsaturated FAs (MUFAs), and tumor necrosis factor alpha-receptor II (TNF-RII) increased (P < 0.05 for all). From chemo-4 to 6M post-chemo, FAs did not change significantly; however, interleukin-6 (IL-6) and IL-8 increased (P < 0.05). From baseline to 6M post-chemo, C20:0 significantly decreased (P < 0.05) while C18:1n9, C20:1n9, total n-9 FAs, total MUFAs significantly increased (P < 0.05 for all); additionally, the n-3/n-6 ratio and IL-6 significantly increased (P < 0.05 for all). Conclusions There were significant changes in serum FAs and serum cytokines in women with breast cancer undergoing chemotherapy. Cytokine changes were consistent with a more inflammatory profile during and after chemotherapy. Future research will investigate associations between serum FAs and serum inflammatory markers in breast cancer survivors undergoing chemotherapy. Funding Sources The Ohio State University Stefanie Spielman Breast Cancer Center Kroger Fund.

321 Phase I clinical trial assessing the combination of systemic chemokine modulatory regimen targeting TLR3 with neoadjuvant chemotherapy in triple negative breast cancer

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A347-A347
Author(s):  
Shipra Gandhi ◽  
Mateusz Opyrchal ◽  
Cayla Ford ◽  
Victoria Fitzpatrick ◽  
Melissa Grimm ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Phase I ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Early Stage ◽  
Standard Dose ◽  
Surrogate Marker ◽  
Comprehensive Cancer Center ◽  
Cancer Center

BackgroundNeoadjuvant chemotherapy (NAC) with taxanes is the standard of care in triple negative breast cancer (TNBC). Intratumoral prevalence of CD8+ cytotoxic T-lymphocytes (CTLs) is associated with an improvement in relapse-free survival (RFS) and overall survival (OS), while regulatory T-cells (Treg) and myeloid derived suppressor cells (MDSC) are associated with poor survival. Higher ratio of CTL/Treg is associated with higher probability of obtaining pathological complete response (pCR), a surrogate marker for RFS. Intratumoral production of CCL5, CXCL9, CXCL10 and CXCL11 is critical for local infiltration with CTLs, while CCL22 is responsible for Treg attraction. Previous studies have shown that CXCL9 expression in the pre-treatment breast tissue is associated with a three-fold higher rate of achieving pCR. Our preclinical data show that Chemokine modulating (CKM) regimen, combining rintatolimod (TLR3 agonist), interferon (IFN)-α2b, and celecoxib (COX-2 inhibitor) increases CTL-attracting, and decreases MDSC-, Treg-favoring chemokines, increasing CTL/Treg ratio in tumor microenvironment, with preferential tumor tissue activation than adjacent healthy tissues. We hypothesize that the combination of CKM with paclitaxel will result in infiltration of TNBC with CTLs, and along with doxorubicin/cyclophosphamide (AC), result in higher pCR, translating into improved RFS and OS.MethodsIn this phase I study NCT04081389, eligibility includes age ≥18 years, confirmed resectable TNBC, radiographically measurable disease ≥1 cm, ECOG PS ≤ 2, adequate organ and marrow function. Patients with autoimmune disease, serious mood disorders, invasive carcinoma within 3 years, history of peptic ulcers or hypersensitivity to NSAIDs will be excluded. We plan to treat three patients with early stage TNBC with paclitaxel 80 mg/m2 IV weekly for 12 weeks, rintatolimod 200 mg IV, celecoxib 200 mg oral twice daily, and accelerated titration of IFN-α2b at doses 0, 5, or 10 million units (MU)/m2 [Dose Levels (DL) 1, 2 and 3 respectively] on days 1–3 (no intra-patient dose escalation) in weeks 1–3. Dose-limiting toxicity (DLT) is defined as grade 3 or higher toxicities within the first 3 weeks. Any DLT will mandate recruitment per the 3+3 model. If no DLT, three patients will be enrolled at DL 4 at 20 MU/m2 IFN- α2b. This will be followed by standard dose-dense AC, and then surgery. The primary endpoint is safety and tolerability of combination and to identify the appropriate DL of CKM and paclitaxel for extended efficacy study. The secondary endpoints include investigation of efficacy (pCR and breast MRI response), along with RFS and OS. Intratumoral biomarkers will be analyzed in an exploratory manner.ResultsN/AConclusionsN/ATrial RegistrationNCT04081389Ethics ApprovalThe study was approved by Roswell Park Comprehensive Cancer Center Institution’s Ethics Board, approval number I-73718.

Plasma glycerophospholipid profile, erythrocyte n–3 PUFAs, and metabolic syndrome incidence: a prospective study in Chinese men and women

2021 ◽  
Author(s):  
Shuangshuang Chen ◽  
Qingqing Wu ◽  
Li Zhu ◽  
Geng Zong ◽  
Huaixing Li ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Fatty Acids ◽  
Polyunsaturated Fatty Acids ◽  
Animal Studies ◽  
Plasma Concentrations ◽  
Positive Association ◽  
Community Dwelling ◽  
P Value ◽  
Total N ◽  
Long Chain

ABSTRACT Background Animal studies have highlighted critical roles of glycerophospholipid (GP) metabolism in various metabolic syndrome (MetS)-related features such as dyslipidemia, obesity, and insulin resistance. However, human prospective studies of associations between circulating GPs and risks of MetS are scarce. Objectives We aimed to investigate whether GPs are associated with incidence of MetS in a well-established cohort. Methods A total of 1243 community-dwelling Chinese aged 50–70 y without MetS at baseline and followed up for 6 y were included in current analyses. A total of 145 plasma GPs were quantified by high-throughput targeted lipidomics. MetS was defined using the updated National Cholesterol Education Program Adult Treatment Panel III criteria for Asian Americans. Results After 6 y, 429 participants developed MetS. Eleven GPs, especially those with long-chain polyunsaturated fatty acids (LCPUFAs) or very-long-chain polyunsaturated fatty acids (VLCPUFAs) at the sn-2 position, including 1 phosphatidylcholine (PC) [PC(18:0/22:6)], 9 phosphatidylethanolamines (PEs) [PE(16:0/22:6), PE(18:0/14:0), PE(18:0/18:1), PE(18:0/18:2), PE(18:0/20:3), PE(18:0/22:5), PE(18:0/22:6), PE(18:1/22:6), and PE(18:2/22:6)], and 1 phosphatidylserine (PS) [PS(18:0/18:0)], were positively associated with incident MetS (RRs: 1.16–1.30 per SD change; Bonferroni-corrected P < 0.05). In network analysis, the strongest positive association for MetS incidence was evidenced in a module mainly composed of PEs containing C22:6 and PSs [RR: 1.21; 95% CI: 1.12, 1.31 per SD change; Bonferroni-corrected P < 0.05]. This association was more pronounced in participants with lower erythrocyte total n–3 PUFA concentrations [Bonferroni-corrected Pinter(P value for the interaction)< 0.05]. Conclusions Elevated plasma concentrations of GPs, especially PEs with LCPUFAs or VLCPUFAs at the sn-2 position, are associated with higher risk of incident MetS. Future studies are merited to confirm our findings.

Survival outcomes in patients with IDC and ILC breast cancer: A well matched single institution study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13056-e13056
Author(s):  
Michael Grimm ◽  
Bhuvaneswari Ramaswamy ◽  
Maryam B. Lustberg ◽  
Robert Wesolowski ◽  
Sagar D. Sardesai ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Metastatic Breast ◽  
Comprehensive Cancer Center ◽  
Cancer Center ◽  
Her2 Status ◽  
Single Institution ◽  
First Line ◽  
Response To Chemotherapy ◽  
Significant Difference

e13056 Background: Invasive lobular carcinoma (ILC) accounts for only 10-15% of all invasive breast cancers but has distinct clinicopathologic characteristics and genomic profiles. In particular, metastatic lobular cancers (mILC) have unique sites of metastasis and it is unclear if the response to initial endocrine therapy differs from metastatic ductal cancers (mIDC). Therefore we have undertaken a single-institution, retrospective analysis to compare overall outcomes and response to initial endocrine therapy (ET) in patients (pts) with metastatic ILC and IDC. Methods: An IRB approved retrospective review of medical records was conducted evaluating pts treated for metastatic IDC and ILC at The Ohio State University Comprehensive Cancer Center from January 1, 2004 to December 31, 2014. Pts diagnosed with mIDC were matched on age, year of diagnosis, estrogen receptor/progesterone receptor and HER2 status and site of metastasis 2:1 to patients diagnosed with mILC. Overall survival (OS) was defined as the time from metastasis to death or last known follow-up. Progression-free survival (PFS) was defined as time from metastasis to progression on first-line ET. Time to chemotherapy (TTC) was defined as time from starting ET for metastasis to initiation of chemotherapy. Kaplan Meier (KM) methods were used to calculate median OS, PFS and TTC. Results: A total of one hundred sixty one pts with metastatic breast cancer were included in this analysis. The demographic features between the two groups were well balanced and included in the table below. The median OS was 2.6 yrs (95% CI: 1.55, 3.22) for mILC and 2.2 yrs (95% CI: 1.95, 2.62) for mIDC. A subset of 111 patients who started on endocrine therapy were used in the PFS and TTC analyses. The median PFS following first-line ET was 2.2 yrs (95% CI: 0.1.0, 2.7) for mILC and 1.4 yrs (95% CI: 0.91, 1.90) for mIDC. Median TTC was 2.1 yrs (95% CI: 1.71, 4.92) for mILC and 2.4 yrs (95% CI: 1.90, 4.77) for mIDC. There was no statistically significant difference in outcomes between the two groups. Conclusions: Outcomes in patients with ILC and IDC have been varied, with several studies reporting that patients with ILC have worse outcomes and response to chemotherapy. Our retrospective study examining outcomes in mILC in comparison with mIDC showed no difference in OS. Given the concern of resistance to conventional therapies in patients with lobular cancers, it is reassuring to see that the median PFS on first line ET and TTC was similar to metastatic ductal cancers.[Table: see text]

scholarly journals The same rat Δ6-desaturase not only acts on 18- but also on 24-carbon fatty acids in very-long-chain polyunsaturated fatty acid biosynthesis

2002 ◽  
Vol 364 (1) ◽  
pp. 49-55 ◽  
Author(s):  
Sabine D'ANDREA ◽  
Hervé GUILLOU ◽  
Sophie JAN ◽  
Daniel CATHELINE ◽  
Jean-Noël THIBAULT ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Polyunsaturated Fatty Acid ◽  
Unsaturated Fatty Acids ◽  
Fatty Acid Biosynthesis ◽  
Chain Polyunsaturated Fatty Acid ◽  
Acid Biosynthesis ◽  
Highly Unsaturated Fatty Acids ◽  
Long Chain ◽  
Δ6 Desaturase

The recently cloned Δ6-desaturase is known to catalyse the first step in very-long-chain polyunsaturated fatty acid biosynthesis, i.e. the desaturation of linoleic and α-linolenic acids. The hypothesis that this enzyme could also catalyse the terminal desaturation step, i.e. the desaturation of 24-carbon highly unsaturated fatty acids, has never been elucidated. To test this hypothesis, the activity of rat Δ6-desaturase expressed in COS-7 cells was investigated. Recombinant Δ6-desaturase expression was analysed by Western blot, revealing a single band at 45kDa. The putative involvement of this enzyme in the Δ6-desaturation of C24:5n-3 to C24:6n-3 was measured by incubating transfected cells with C22:5n-3. Whereas both transfected and non-transfected COS-7 cells were able to synthesize C24:5n-3 by elongation of C22:5n-3, only cells expressing Δ6-desaturase were also able to produce C24:6n-3. In addition, Δ6-desaturation of [1-14C]C24:5n-3 was assayed invitro in homogenates from COS-7 cells expressing Δ6-desaturase or not, showing that Δ6-desaturase catalyses the conversion of C24:5n-3 to C24:6n-3. Evidence is therefore presented that the same rat Δ6-desaturase catalyses not only the conversion of C18:3n-3 to C18:4n-3, but also the conversion of C24:5n-3 to C24:6n-3. A similar mechanism in the n-6 series is strongly suggested.

The effect of long-chain polyunsaturated fatty acid and vitamin E supplementation of ewes on neonatal lamb vigour, lamb growth and colostrum parameters

2002 ◽  
Vol 2002 ◽  
pp. 7-7 ◽  
Author(s):  
J. L. Capper ◽  
R. G. Wilkinson ◽  
L. A. Sinclair ◽  
S. E. Pattinson ◽  
A. M. Mackenzie
Keyword(s):  
Fatty Acids ◽  
Vitamin E ◽  
Chain Polyunsaturated Fatty Acid ◽  
Alpha Linolenic Acid ◽  
Chain Pufa ◽  
Ruminant Diets ◽  
The Brain ◽  
Lamb Growth ◽  
Long Chain ◽  
Vitamin E Supplementation

The long-chain polyunsaturated fatty acids (PUFA) docosahexaenoic acid (DHA) and arachidonic acid (AA) are the most abundant fatty acids in the brain and are vital for its correct development and for that of the nervous system (Huang and Craig-Schmidt, 1996). Ruminant diets are low in DHA and its precursor alpha-linolenic acid. In addition, dietary PUFAs are substantially hydrogenated in the rumen. Consequently, it may be argued that the diets of pregnant and lactating ewes may be deficient in DHA and that a response to supplementation may be observed. Studies involving the supplementation of pregnant ewes with supraoptimal levels of vitamin E have shown that lambs born to supplemented dams are more vigorous immediately after birth and have higher liveweight gains (Merrell, 1998). The objective of this experiment was to investigate the effects of dietary long-chain PUFA in combination with vitamin E supplementation of ewes on ewe and lamb performance.

scholarly journals Erythrocyte Long Chain Omega 3 Fatty Acids Are Associated with Higher Lean Mass in Postmenopausal Women Newly Diagnosed with Breast Cancer (P05-024-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Martha Belury ◽  
Rachel Cole ◽  
Rebecca Andridge ◽  
Qing Xie ◽  
Ashleigh Keiter ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Skeletal Muscle ◽  
Fatty Acids ◽  
Body Composition ◽  
Lean Mass ◽  
Cardiometabolic Health ◽  
Omega 3 ◽  
Appendicular Lean Mass ◽  
Muscle Health ◽  
Long Chain

Abstract Objectives Cancer contributes to adverse changes in body composition that may increase risk of cardiometabolic diseases. Skeletal muscle is a main driver of cardiometabolic health. We hypothesize that higher intake of long chain omega-3 polyunsaturated fatty acids (LCn3PUFAs) is associated with muscle health. This study evaluates whether LCn3PUFA exposure assessed in diet and in blood is associated with markers of muscle health in women with breast cancer. Methods This is a cross-sectional analysis evaluating LCn3PUFA exposure and markers of muscle health in women (N = 150) prior to treatment for breast cancer. Exposure to LCn3PUFAs was assessed by a diet history questionnaire (DHQ), a question specifically about supplement usage and biomarker of LCn3PUFAs in red blood cells (RBC). Body composition were measured at the same visit using dual x-ray absorptiometry. Linear regression models were used to test for associations. Results 13% (N = 19) of women reported using fish oil supplements (e.g., Supplement Users) and had significantly higher levels of RBC LCn3PUFAs than Supplement Non-users. In Supplement Non-users, there was a positive association between reported dietary exposure by DHQ and RBC LCn3PUFA levels. The n3 index (e.g., sum of RBC EPA + DHA) and DHA (22:6n3) were positively associated with appendicular lean mass/BMI. There were no significant correlations between RBC LCn3PUFAs with grip strength and or other measurements of body composition. Conclusions As a biomarker of intake, RBC LCn3PUFAs are positively associated with appendicular lean mass, a measure of skeletal muscle mass. A future study should prospectively evaluate whether higher LCn3PUFA exposure (as measured in blood) is associated with maintaining better muscle health during and following cancer treatment. Funding Sources Funding was provided by the National Cattleman's Beef Association, NIH (JKG) CA186720, Ohio Agriculture Research and Development Center and the Carol S. Kennedy Professorship.

High Level of Esterification of Steroids to Long-Chain Fatty Acids in ZR-75-1 Human Breast Cancer Cells

1990 ◽  
Vol 595 (1 Steroid Forma) ◽  
pp. 422-424
Author(s):  
Donald Poirier ◽  
Richard Poulin ◽  
Yves Mérand ◽  
Catherine Thériault ◽  
Fernand Labrie
Keyword(s):  
Breast Cancer ◽  
Fatty Acids ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Long Chain Fatty Acids ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
High Level ◽  
Long Chain
Sign in / Sign up

Export Citation Format

Share Document