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Article ; Online: Relationships between Breast Feeding and Breast Cancer Subtypes: Lessons Learned from Studies in Humans and in Mice.

Ambrosone, Christine B / Higgins, Michael J

2020 Volume 80, Issue 22, Page(s) 4871–4877

Abstract: There are differential risk relationships between parity and breast cancer according to estrogen receptor (ER) status, with an increased risk of ... ...

Abstract	There are differential risk relationships between parity and breast cancer according to estrogen receptor (ER) status, with an increased risk of ER
MeSH term(s)	African Americans ; Age Factors ; Animals ; Breast/growth & development ; Breast/physiology ; Breast Feeding ; Breast Neoplasms/chemistry ; Breast Neoplasms/etiology ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; DNA Methylation ; Epigenesis, Genetic ; Female ; GATA3 Transcription Factor/metabolism ; Hepatocyte Nuclear Factor 3-alpha/metabolism ; Humans ; Insulin-Like Growth Factor Binding Protein 5/metabolism ; Menarche ; Mice ; Neoplasms, Radiation-Induced/etiology ; Parity/physiology ; Pregnancy ; Pregnancy-Associated Plasma Protein-A/genetics ; Pregnancy-Associated Plasma Protein-A/metabolism ; Receptor, ErbB-2 ; Receptors, Estrogen ; Receptors, Progesterone ; Risk ; Stem Cells/radiation effects ; Triple Negative Breast Neoplasms/chemistry
Chemical Substances	FOXA1 protein, human ; GATA3 Transcription Factor ; GATA3 protein, human ; Hepatocyte Nuclear Factor 3-alpha ; IGFBP5 protein, human ; Insulin-Like Growth Factor Binding Protein 5 ; Receptors, Estrogen ; Receptors, Progesterone ; ERBB2 protein, human (EC 2.7.10.1) ; Receptor, ErbB-2 (EC 2.7.10.1) ; Pregnancy-Associated Plasma Protein-A (EC 3.4.24.-) ; PAPPA protein, human (EC 3.4.24.79)
Language	English
Publishing date	2020-08-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-20-0077
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Article ; Online: Reply to E. Javor et al.

Ambrosone, Christine B / Hutson, Alan D

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

2020 Volume 38, Issue 18, Page(s) 2111

MeSH term(s)	Breast Neoplasms ; Dietary Supplements ; Humans
Language	English
Publishing date	2020-04-21
Publishing country	United States
Document type	Letter ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	604914-x
ISSN	1527-7755 ; 0732-183X
ISSN (online)	1527-7755
ISSN	0732-183X
DOI	10.1200/JCO.20.00546
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Article ; Online: Urinary Concentrations of Triclosan, Bisphenol A, and Brominated Flame Retardants and the Association of Triclosan with Demographic Characteristics and Body Fatness among Women with Newly Diagnosed Breast Cancer.

Ilozumba, Mmadili N / Shelver, Weilin L / Hong, Chi-Chen / Ambrosone, Christine B / Cheng, Ting-Yuan David

International journal of environmental research and public health

2022 Volume 19, Issue 8

Abstract: Background: Triclosan, bisphenol A (BPA), and brominated flame retardants are environmental estrogenic endocrine-disrupting compounds that may influence the prognosis of breast cancer. We examined the urinary concentrations of these compounds and their ... ...

Abstract	Background: Triclosan, bisphenol A (BPA), and brominated flame retardants are environmental estrogenic endocrine-disrupting compounds that may influence the prognosis of breast cancer. We examined the urinary concentrations of these compounds and their associations with demographic characteristics and body fatness in a population of women with newly diagnosed breast cancer. Methods: Overnight urine collection and anthropometric measures were obtained from 302 participants. Triclosan, BPA, tetrabromobisphenol A (TBBPA), and tetrabromobenzoic acid (TBBA) concentrations were determined using ultra-performance liquid chromatography−tandem mass spectrometry. Regression analyses were conducted to examine associations of urinary compound concentration with age, menopause, race, ethnicity, educational level, estrogen receptor status, body size, and body composition. Results: Triclosan, BPA, and TBBA were detected in urine samples from 98.3%, 6.0%, and 0.3% of patients, respectively; TBBPA was undetectable. Among patients with quantifiable values, the geometric mean concentrations were 20.74 µg/L (27.04 µg/g creatinine) for triclosan and 0.82 µg/L (1.08 µg/g creatinine) for BPA. Body mass index ≥ 30 vs. <25 kg/m2 was associated with lower creatinine-corrected urinary concentrations of triclosan (−40.00, 95% confidence interval [CI] = −77.19 to −2.81; p = 0.0351). The observed association was predominantly in postmenopausal women (−66.57; 95% CI: −109.18% to −23.96%). Consistent results were found for associations between triclosan levels and fat mass variables. Conclusion: In this study population, women with newly diagnosed breast cancer had triclosan exposure. Assessments of the implications of urinary concentrations of triclosan for women should consider body fatness and menopausal status.
MeSH term(s)	Benzhydryl Compounds/urine ; Breast Neoplasms/epidemiology ; Creatinine ; Demography ; Female ; Flame Retardants ; Humans ; Male ; Phenols ; Triclosan/urine
Chemical Substances	Benzhydryl Compounds ; Flame Retardants ; Phenols ; Triclosan (4NM5039Y5X) ; Creatinine (AYI8EX34EU) ; bisphenol A (MLT3645I99)
Language	English
Publishing date	2022-04-13
Publishing country	Switzerland
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2175195-X
ISSN	1660-4601 ; 1661-7827
ISSN (online)	1660-4601
ISSN	1661-7827
DOI	10.3390/ijerph19084681
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Article ; Online: A biopsychosocial model to understand racial disparities in the era of cancer immunotherapy.

Yao, Song / Ambrosone, Christine B / Osarogiagbon, Raymond U / Morrow, Gary R / Kamen, Charles

Trends in cancer

2022 Volume 9, Issue 1, Page(s) 6–8

Abstract: The approval and wide uptake of immune checkpoint inhibitors (ICIs) in oncology practice raise the concerns of possibly worsened racial disparities in cancer treatment due to biological and psychosocial reasons. We propose a multilevel biopsychosocial ... ...

Abstract	The approval and wide uptake of immune checkpoint inhibitors (ICIs) in oncology practice raise the concerns of possibly worsened racial disparities in cancer treatment due to biological and psychosocial reasons. We propose a multilevel biopsychosocial model to understand the opportunities and challenges to racial disparities in the era of cancer immunotherapy.
MeSH term(s)	Humans ; Models, Biopsychosocial ; Immunotherapy ; Neoplasms/drug therapy
Language	English
Publishing date	2022-10-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2852626-0
ISSN	2405-8025 ; 2405-8033 ; 2405-8033
ISSN (online)	2405-8025 ; 2405-8033
ISSN	2405-8033
DOI	10.1016/j.trecan.2022.10.002
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Article: DNA methylation differences in noncoding regions in ER negative breast tumors between Black and White women.

Chen, Jianhong / Higgins, Michael J / Hu, Qiang / Khoury, Thaer / Liu, Song / Ambrosone, Christine B / Gong, Zhihong

Frontiers in oncology

2023 Volume 13, Page(s) 1167815

Abstract: Introduction: Incidence of estrogen receptor (ER)-negative breast cancer, an aggressive tumor subtype associated with worse prognosis, is higher among African American/Black women than other US racial and ethnic groups. The reasons for this disparity ... ...

Abstract	Introduction: Incidence of estrogen receptor (ER)-negative breast cancer, an aggressive tumor subtype associated with worse prognosis, is higher among African American/Black women than other US racial and ethnic groups. The reasons for this disparity remain poorly understood but may be partially explained by differences in the epigenetic landscape. Methods: We previously conducted genome-wide DNA methylation profiling of ER- breast tumors from Black and White women and identified a large number of differentially methylated loci (DML) by race. Our initial analysis focused on DML mapping to protein-coding genes. In this study, motivated by increasing appreciation for the biological importance of the non-protein coding genome, we focused on 96 DMLs mapping to intergenic and noncoding RNA regions, using paired Illumina Infinium Human Methylation 450K array and RNA-seq data to assess the relationship between CpG methylation and RNA expression of genes located up to 1Mb away from the CpG site. Results: Twenty-three (23) DMLs were significantly correlated with the expression of 36 genes (FDR<0.05), with some DMLs associated with the expression of single gene and others associated with more than one gene. One DML (cg20401567), hypermethylated in ER- tumors from Black versus White women, mapped to a putative enhancer/super-enhancer element located 1.3 Kb downstream of Discussion: Our findings indicate that epigenetic differences in ER- tumors between Black and White women are linked to altered gene expression and may hold functional significance in breast cancer pathogenesis.
Language	English
Publishing date	2023-05-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2023.1167815
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Article: A polygenic score associated with fracture risk in breast cancer patients treated with aromatase inhibitors.

Hook, Christine / Chatterjee, Udit / Sheng, Haiyang / Zhu, Qianqian / Robinson, Timothy / Roh, Janise M / Laurent, Cecile A / Lee, Catherine / Delmerico, Jennifer / Lo, Joan C / Ambrosone, Christine B / Kushi, Lawrence H / Kwan, Marilyn L / Yao, Song

NPJ breast cancer

2024 Volume 10, Issue 1, Page(s) 9

Abstract: Identifying women at high risk of osteoporotic fracture from aromatase inhibitor (AI) therapy for breast cancer is largely based on known risk factors for healthy postmenopausal women, which might not accurately reflect the risk in breast cancer patients ...

Abstract	Identifying women at high risk of osteoporotic fracture from aromatase inhibitor (AI) therapy for breast cancer is largely based on known risk factors for healthy postmenopausal women, which might not accurately reflect the risk in breast cancer patients post-AI therapy. To determine whether a polygenic score associated with fracture in healthy women is also significant in women treated with AIs for breast cancer, we used data from a prospective observational cohort of 2152 women diagnosed with hormonal receptor positive breast cancer treated with AIs as the initial endocrine therapy and examined a polygenic score of heel quantitative ultrasound speed of sound (gSOS) in relation to incident osteoporotic fracture after AI therapy during a median 6.1 years of follow up after AI initiation. In multivariable models, patients with the second and third highest tertiles (T) versus the lowest tertile of gSOS had significantly lower risk of fracture (T2: adjusted HR = 0.61, 95% CI: 0.46-0.80; T3: adjusted HR = 0.53, 95% CI: 0.40-0.70). The lower risk of fracture in patients with the highest tertile of gSOS remained significant after further adjustment for BMD at the hip (T3: adjusted HR = 0.62, 95% CI: 0.42-0.91). In conclusion, our analysis showed gSOS as a novel genetic predictor for fracture risk independent of BMD among breast cancer patients treated with AIs. Future studies are warranted to evaluate the performance of incorporating gSOS in prediction models for the risk of AI-related fracture in breast cancer patients.
Language	English
Publishing date	2024-01-20
Publishing country	United States
Document type	Journal Article
ISSN	2374-4677
ISSN	2374-4677
DOI	10.1038/s41523-024-00615-9
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Article ; Online: Differential methylation and expression patterns of microRNAs in relation to breast cancer subtypes among American women of African and European ancestry.

Gong, Zhihong / Chen, Jianhong / Wang, Jie / Liu, Song / Ambrosone, Christine B / Higgins, Michael J

PloS one

2021 Volume 16, Issue 3, Page(s) e0249229

Abstract: Aggressive high-grade, estrogen receptor negative (ER-) breast cancer is more common among American women of African ancestry (AA) than those of European ancestry (EA). Epigenetic mechanisms, particularly DNA methylation and altered microRNA (miRNA) ... ...

Abstract	Aggressive high-grade, estrogen receptor negative (ER-) breast cancer is more common among American women of African ancestry (AA) than those of European ancestry (EA). Epigenetic mechanisms, particularly DNA methylation and altered microRNA (miRNA) expression, may contribute to racial differences in breast cancer. However, few studies have specifically characterized genome-wide DNA methylation-based modifications at the miRNA level in relation to ER+ and ER- subtype, and their functional role in the regulation of miRNA expression, especially among high risk AA women. In this study, we evaluated DNA methylation patterns of miRNA encoding genes and their effect on expression in breast tumors from both AA and EA women. The genome-wide methylation screen identified a total of 7,191 unique CpGs mapped to 1,292 miRNA genes, corresponding to 2,035 unique mature miRNAs. We identified differentially methylated loci (DMLs: (\|delta β\|)>0.10, FDR<0.05) between ER- and ER+ tumor subtypes, including 290 DMLs shared in both races, 317 and 136 were specific to AA and EA women, respectively. Integrated analysis identified certain DMLs whose methylation levels were significantly correlated with the expression of relevant miRNAs, such as multiple CpGs within miR-190b and miR-135b highly negatively correlated with their expression. These results were then validated in the TCGA dataset. Target prediction and pathway analysis showed that these DNA methylation-dysregulated miRNAs are involved in multiple cancer-related pathways, including cell cycle G1-S growth factor regulation, cytoskeleton remodeling, angiogenesis, EMT, and ESR1-mediated signaling pathways. In summary, our results suggest that DNA methylation changes within miRNA genes are associated with altered miRNA expression, which may contribute to the network of subtype- and race-related tumor biological differences in breast cancer. These findings support the involvement of epigenetic regulation of miRNA expression and provide insights into the relations of clinical-relevant miRNAs to their target genes, which may serve as potential preventative and therapeutic targets.
MeSH term(s)	African Americans/genetics ; Breast Neoplasms/genetics ; Epigenesis, Genetic ; European Continental Ancestry Group/genetics ; Female ; Gene Expression Profiling ; Humans ; Methylation ; MicroRNAs/genetics ; Middle Aged ; United States/epidemiology ; United States/ethnology
Chemical Substances	MicroRNAs
Language	English
Publishing date	2021-03-30
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0249229
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Article ; Online: Clinical, Epidemiologic, and Pathologic Significance of ERBB2-Low Expression in Breast Cancer.

Khoury, Thaer / Mendicino, Lucas / Payne Ondracek, Rochelle / Yao, Song / Davis, Warren / Omilian, Angela R / Kwan, Marilyn L / Roh, Janise M / D'Addario, Lia / Valice, Emily / Fernandez, Daniel / Ergas, Isaac J / Chua, Alfredo V / Ambrosone, Christine B / Kushi, Lawrence H

JAMA network open

2024 Volume 7, Issue 3, Page(s) e243345

Abstract: Importance: It is unclear whether breast cancer (BC) with low ERBB2 expression (ERBB2-low) is a distinct clinical, pathological, and epidemiological entity from BC classified as no ERBB2 expression (ERBB2-negative).: Objective: To evaluate the ... ...

Abstract	Importance: It is unclear whether breast cancer (BC) with low ERBB2 expression (ERBB2-low) is a distinct clinical, pathological, and epidemiological entity from BC classified as no ERBB2 expression (ERBB2-negative). Objective: To evaluate the clinical, pathological, and epidemiologic features of BC with ERBB2-low expression compared with ERBB2-negative BC in a large population study. Design, setting, and participants: This cohort study was conducted as part of the Pathways Study, a prospective, racially and ethnically diverse cohort study of women with BC enrolled between 2006 and 2013 in Kaiser Permanente Northern California (KPNC). The hematoxylin and eosin slides underwent centralized pathology review, including the percentage of tumor infiltrating lymphocytes (TILs). Breast biomarker results were extracted from pathology reports, and women were included if they had a documented ERBB2 value that was not classified ERBB2-positive. Data were analyzed from February 2023 through January 2024. Exposure: Clinical and tumor characteristics associated with BC and ERBB2-low or ERBB2-negative status. Main outcome and measures: ERBB2-low was defined as immunohistochemistry score of 1+ or 2+ (negative by in situ hybridization); ERBB2-negative was defined as immunohistochemistry score of 0+. Other data were collected by self-report or extraction from electronic health records, including BC risk factors, tumor characteristics, treatment modality, and survival outcomes, with recurrence-free survival (RFS) as the primary outcome and overall survival (OS) and BC-specific mortality (BCSM) as secondary outcomes. The clinical, pathological, and epidemiological variables were compared between ERBB2-low and ERBB2-negative BC. Results: Of 2200 eligible patients (all female; with mean [SD] age, 60.4 [11.9] years), 1295 (57.2%) had tumors that were ERBB2-low. Hormone receptors were positive in 1956 patients (88.9%). The sample included 291 Asian patients (13.2%), 166 Black patients (7.5%), 253 Hispanic patients (11.5%), 1439 White patients (65.4%), and 51 patients (2.3%) who identified as other race or ethnicity (eg, American Indian or Alaska Native and Pacific Islander). Within the hormone receptor-negative group, patients whose tumors had ERBB2-low staining, compared with those with ERBB2-negative tumors, had better OS (hazard ratio [HR], 0.54; 95% CI, 0.33-0.91; P = .02), RFS (HR, 0.53; 95% CI, 0.30-0.95; P = .03), and BCSM (HR, 0.43; 95% CI, 0.22-0.84; P = .01). In multivariable survival analysis stratified by hormone receptor status and adjusted for key covariates, patients with ERBB2-low and hormone receptor-negative tumors had lower overall mortality (HR, 0.48; 95% CI, 0.27-0.83; P = .009), RFS (HR, 0.45; 95% CI, 0.24-0.86; P = .02), and BCSM (subdistribution HR, 0.21; 95% CI, 0.10-0.46; P < .001) compared with patients with ERBB2-negative and hormone receptor-negative tumors. Within the hormone receptor-negative subtype, patients with ERBB2-low and high TILs tumors had better survival across all 3 outcomes compared with patients with ERBB2-negative and low TILs tumors. Additionally, patients with ERBB2-low and low TILs tumors had better BCSM (subdistribution HR, 0.36; 95% CI, 0.14-0.92; P = .03). Conclusions and relevance: These findings suggest that there were clinical, pathological, and epidemiological differences between ERBB2-low and ERBB2-negative BC, raising the possibility that ERBB2-low might be a unique biologic entity.
MeSH term(s)	Female ; Humans ; Middle Aged ; Breast Neoplasms/drug therapy ; Cohort Studies ; Hormones/therapeutic use ; Lymphocytes, Tumor-Infiltrating ; Prospective Studies ; Receptor, ErbB-2 ; Aged
Chemical Substances	ERBB2 protein, human (EC 2.7.10.1) ; Hormones ; Receptor, ErbB-2 (EC 2.7.10.1)
Language	English
Publishing date	2024-03-04
Publishing country	United States
Document type	Journal Article
ISSN	2574-3805
ISSN (online)	2574-3805
DOI	10.1001/jamanetworkopen.2024.3345
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Article ; Online: Modifying Effects of Genetic Variations on the Association Between Dietary Isothiocyanate Exposure and Non-muscle Invasive Bladder Cancer Prognosis in the Be-Well Study.

Wang, Zinian / Kwan, Marilyn L / Haque, Reina / Singh, Prashant K / Goniewicz, Maciej / Pratt, Rachel / Lee, Valerie S / Roh, Janise M / Ergas, Isaac J / Cannavale, Kimberly L / Loo, Ronald K / Aaronson, David S / Quesenberry, Charles P / Zhang, Yuesheng / Ambrosone, Christine B / Kushi, Lawrence H / Tang, Li

Molecular nutrition & food research

2024 Volume 68, Issue 8, Page(s) e2400087

Abstract: Scope: Dietary isothiocyanate (ITC) exposure from cruciferous vegetable (CV) intake may improve non-muscle invasive bladder cancer (NMIBC) prognosis. This study aims to investigate whether genetic variations in key ITC-metabolizing/functioning genes ... ...

Abstract	Scope: Dietary isothiocyanate (ITC) exposure from cruciferous vegetable (CV) intake may improve non-muscle invasive bladder cancer (NMIBC) prognosis. This study aims to investigate whether genetic variations in key ITC-metabolizing/functioning genes modify the associations between dietary ITC exposure and NMIBC prognosis outcomes. Methods and results: In the Bladder Cancer Epidemiology, Wellness, and Lifestyle Study (Be-Well Study), a prospective cohort of 1472 incident NMIBC patients, dietary ITC exposure is assessed by self-reported CV intake and measured in plasma ITC-albumin adducts. Using Cox proportional hazards regression models, stratified by single nucleotide polymorphisms (SNPs) in nine key ITC-metabolizing/functioning genes, it is calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for recurrence and progression. The rs15561 in N-acetyltransferase 1 (NAT1) is alter the association between CV intake and progression risk. Multiple SNPs in nuclear factor E2-related factor 2 (NRF2) and nuclear factor kappa B (NFκB) are modify the associations between plasma ITC-albumin adduct level and progression risk (p Conclusion: Despite that genetic variations in ITC-metabolizing/functioning genes may modify the effect of dietary ITCs on NMIBC prognosis, dietary recommendation of CV consumption may help improve NMIBC survivorship.
MeSH term(s)	Humans ; Urinary Bladder Neoplasms/genetics ; Urinary Bladder Neoplasms/pathology ; Male ; Female ; Isothiocyanates/pharmacology ; Isothiocyanates/administration & dosage ; Polymorphism, Single Nucleotide ; Middle Aged ; Prognosis ; Aged ; Prospective Studies ; Diet ; NF-E2-Related Factor 2/genetics ; NF-E2-Related Factor 2/metabolism ; Arylamine N-Acetyltransferase/genetics ; Non-Muscle Invasive Bladder Neoplasms
Chemical Substances	Isothiocyanates ; NF-E2-Related Factor 2 ; Arylamine N-Acetyltransferase (EC 2.3.1.5) ; NFE2L2 protein, human
Language	English
Publishing date	2024-04-06
Publishing country	Germany
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2160372-8
ISSN	1613-4133 ; 1613-4125
ISSN (online)	1613-4133
ISSN	1613-4125
DOI	10.1002/mnfr.202400087
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Article: Pre-treatment Amino Acids and Risk of Paclitaxel-induced Peripheral Neuropathy in SWOG S0221.

Chen, Ciao-Sin / Zirpoli, Gary / Thomas Budd, G / Barlow, William E / Pusztai, Lajos / Hortobagyi, Gabriel N / Albain, Kathy S / Godwin, Andrew K / Thompson, Alastair / Lynn Henry, N / Ambrosone, Christine B / Stringer, Kathleen A / Hertz, Daniel L

Research square

2023

Abstract: Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a treatment-limiting and debilitating neurotoxicity of many commonly used anti-cancer agents, including paclitaxel. The objective of this study was to confirm the previously found inverse ... ...

Abstract	Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a treatment-limiting and debilitating neurotoxicity of many commonly used anti-cancer agents, including paclitaxel. The objective of this study was to confirm the previously found inverse association between pre-treatment blood concentrations of histidine and CIPN occurrence and examine relationships of other amino acids with CIPN severity. Methods: Pre-treatment levels of 20 amino acid concentrations were measured via a targeted mass spectrometry assay in banked serum from the SWOG S0221 (NCT00070564) trial of patients with early-stage breast cancer receiving paclitaxel. The associations between amino acid levels and CIPN occurrence or severity were tested in regression analysis adjusted for paclitaxel schedule, age, self-reported race, and body mass index with Bonferroni correction for multiple comparisons. The network of metabolic pathways of amino acids was analyzed using over-representation analysis in MetaboAnalyst. The partial correlation network of amino acids was evaluated using a debiased sparse partial correlation algorithm and Cytoscape. Results: In the primary analysis, histidine concentration was not associated with CIPN occurrence (odds ratio (OR) = 0.97 [0.83, 1.13], p = 0.72). In a secondary analysis, no amino acid was associated with CIPN occurrence (all p > 0.0025). Higher concentrations of four amino acids, glutamate (β = 0.58 [0.23, 0.93], p = 0.001), phenylalanine (β = 0.54 [0.19, 0.89], p = 0.002), tyrosine (β = 0.57 [0.23, 0.91], p = 0.001), and valine (β = 0.58 [0.24, 0.92], p = 0.001) were associated with more severe CIPN, but none of these associations retained significance after adjustment. In the over-representation analysis, no amino acid metabolic pathways were significantly enriched (all FDR > 0.05). In the network of enriched pathways, glutamate metabolism had the highest centrality. Conclusions: This analysis showed that pre-treatment serum amino acid concentrations are not strongly predictive of CIPN severity. Future prospectively designed studies that assess non-amino acid metabolomics predictors are encouraged.
Language	English
Publishing date	2023-09-01
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-3242513/v1
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