Intergenerational transmission of sucralose and acesulfame-potassium from mothers to their infants via human milk: a pharmacokinetic study.

Background: Low-calorie sweetener (LCS) consumption is prevalent among lactating mothers, yet infants' exposure to LCS in human milk is not well-characterized.

Objectives: Conduct a pharmacokinetic study of sucralose and acesulfame-potassium (ace-K) in mothers' milk and plasma over 72 h and in infants' plasma.

Methods: Following baseline blood and milk collection, mothers (n = 40) consumed 20 oz of diet cranberry juice containing sucralose and ace-K.

Antibody responses in blood and saliva post COVID-19 bivalent booster do not reveal an Omicron BA.4/BA.5- specific response.

Introduction: Current SARS-CoV-2 strains continue to mutate and attempt to evade the antibody response elicited by previous exposures and vaccinations. In September of 2022, the first updated SARS-CoV-2 vaccines, designed to create immune responses specific for the variants circulating in 2022, were approved. These new vaccines, known commonly as the bivalent boost(er), include mRNA that encodes both the original Wuhan-Hu-1 spike protein as well as the spike protein specific to the Omicron BA.

Mammary epithelium permeability during established lactation: associations with cytokine levels in human milk.

Objective: The cytokine profile of human milk may be a key indicator of mammary gland health and has been linked to infant nutrition, growth, and immune system development. The current study examines the extent to which mammary epithelium permeability (MEP) is associated with cytokine profiles during established lactation within a sample of US mothers.

Methods: Participants were drawn from a previous study of human milk cytokines.

Deciphering a proteomic signature for the early detection of breast cancer from breast milk: the role of quantitative proteomics.

Introduction: Breast cancer is one of the most prevalent cancers among women in the United States. Current research regarding breast milk has been focused on the composition and its role in infant growth and development. There is little information about the proteins, immune cells, and epithelial cells present in breast milk which can be indicative of the emergence of BC cells and tumors.

Rapid cell isolation in breastmilk in a non-clinical setting by a deterministic lateral displacement device and selective water and fat absorption.

Breastmilk is a reliable source of biomarker-containing, sloughed breast cells that have the potential to give valuable health insights to new mothers. Furthermore, known DNA-based markers for pregnancy-associated breast cancer are chemically stable and can be safely stored on a commercially available FTA® Elute Micro (EM) card, which can subsequently be mailed to a testing facility for the cost of a stamp. In theory, this archiving process can be performed by nonprofessionals in very low-resource settings as it simply requires placing a drop of breastmilk on an EM card.

The MILK study: Investigating intergenerational transmission of low-calorie sweeteners in breast milk.

Introduction: Forty-four percent of lactating women in the United States consume beverages containing low calorie sweeteners (LCS), and the presence of LCS in the food supply has continued to increase in recent years. While LCS are approved by the United States Food and Drug Administration (FDA) and are believed to be safe for human consumption, intergenerational LCS transmission and the health impacts of early life LCS exposure are severely understudied.

Methods And Analysis: In a tightly controlled, single site, prospective interventional study, mothers' plasma and breast milk, and infants' plasma will be collected from 40 mother-infant dyads over the course of 72 h, with rich sampling following maternal ingestion of a LCS sweetened beverage containing sucralose and acesulfame potassium (ace-K).

Proteomics analysis of human breast milk by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) coupled with mass spectrometry to assess breast cancer risk.

Breast cancer (BC) is one of the most common cancers and one of the most common causes for cancer-related mortality. Discovery of protein biomarkers associated with cancer is considered important for early diagnosis and prediction of the cancer risk. Protein biomarkers could be investigated by large-scale protein investigation or proteomics, using mass spectrometry (MS)-based techniques.

Mass Spectrometry-Based Proteomics of Human Milk to Identify Differentially Expressed Proteins in Women with Breast Cancer versus Controls.

It is thought that accurate risk assessment and early diagnosis of breast cancer (BC) can help reduce cancer-related mortality. Proteomics analysis of breast milk may provide biomarkers of risk and occult disease. Our group works on the analysis of human milk samples from women with BC and controls to investigate alterations in protein patterns of milk that could be related to BC.

Durable antibody and effector memory T cell responses in breastmilk from women with SARS-CoV-2.

Background: Given that only 25% of pregnant women elect to receive a COVID-19 vaccine, maternal SARS-CoV-2 infection remains an important route of conferring protective passive immunity to breastfed infants of mothers who are not vaccinated.

Methods: We enrolled 30 lactating participants between December 2020 and March 2021 who had a positive PCR-test and their first COVID-19 symptoms within the previous 21 days. Participants were asked to provide serial bilateral milk samples at 12 timepoints (~ every 3 days) over a period of 35 days.

New Moms Wellness Study: the randomized controlled trial study protocol for an intervention study to increase fruit and vegetable intake and lower breast cancer risk through weekly counseling and supplemental fruit and vegetable box delivery in breastfeeding women.

Background: Laboratory studies indicate that chemicals in fruits and vegetables have anti-carcinogenic and anti-inflammatory activities that can lower breast cancer risk. However, epidemiologic studies of the association between fruit and vegetable intake and breast cancer risk have produced mixed results. Measurement error, confounding, and an emphasis on diet in later adulthood may contribute to weak associations.

Neutralizing Antibodies and Cytokines in Breast Milk After Coronavirus Disease 2019 (COVID-19) mRNA Vaccination.

Objective: To evaluate immune responses to coronavirus disease 2019 (COVID-19) mRNA-based vaccines present in breast milk and transfer of the immune responses to breastfeeding infants.

Methods: We enrolled 30 lactating women who received mRNA-based COVID-19 vaccines from January through April 2021 in this cohort study. Women provided serial milk samples, including milk expressed before vaccination, across 2-3 weeks after the first dose, and across 3 weeks after the second dose.

Humoral and Cell-Mediated Immune Response in Colostrum from Women Diagnosed Positive for SARS-CoV-2.

To evaluate the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in colostrum from women who tested positive for the virus. Between March and September 2020 we obtained bilateral colostrum samples collected on spot cards within 48 hours of delivery from 15 new mothers who had previously tested positive for SARS-CoV-2. Four of 15 women provided liquid colostrum, which was used for validating results obtained from spot cards.

Prediagnostic White Blood Cell DNA Methylation and Risk of Breast Cancer in the Prostate Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) Cohort.

Background: White blood cell (WBC) DNA may contain methylation patterns that are associated with subsequent breast cancer risk. Using a high-throughput array and samples collected, on average, 1.3 years prior to diagnosis, a case-cohort analysis nested in the prospective Sister Study identified 250 individual CpG sites that were differentially methylated between breast cancer cases and noncases.

Enrichment of CpG island shore region hypermethylation in epigenetic breast field cancerization.

Unlabelled: While changes in DNA methylation are known to occur early in breast carcinogenesis and the landscape of breast tumour DNA methylation is profoundly altered compared with normal tissue, there have been limited efforts to identify DNA methylation field cancerization effects in histologically normal breast tissue adjacent to tumour. Matched tumour, histologically normal tissue of the ipsilateral breast (ipsilateral-normal), and histologically normal tissue of the contralateral breast (contralateral-normal) were obtained from nine women undergoing bilateral mastectomy. Laser capture microdissection was used to select epithelial cells from normal tissue, and neoplastic cells from tumour for genome-scale measures of DNA methylation with the Illumina HumanMethylationEPIC array.

Inter-Individual Variation in Response to Estrogen in Human Breast Explants.

Exposure to estrogen is strongly associated with increased breast cancer risk. While all women are exposed to estrogen, only 12% are expected to develop breast cancer during their lifetime. These women may be more sensitive to estrogen, as rodent models have demonstrated variability in estrogen sensitivity.

Prediagnostic breast milk DNA methylation alterations in women who develop breast cancer.

Prior candidate gene studies have shown tumor suppressor DNA methylation in breast milk related with history of breast biopsy, an established risk factor for breast cancer. To further establish the utility of breast milk as a tissue-specific biospecimen for investigations of breast carcinogenesis, we measured genome-wide DNA methylation in breast milk from women with and without a diagnosis of breast cancer in two independent cohorts. DNA methylation was assessed using Illumina HumanMethylation450k in 87 breast milk samples.

Polymeric nanoassemblies for enrichment and detection of peptides and proteins in human breast milk.

Human breast milk is an understudied biological fluid that may be useful for early detection of breast cancer. Methods for enriching and detecting biomarkers in human breast milk, however, are not as well-developed as compared with other biological fluids. In this work, we demonstrate a new enrichment method based on polymeric nanoassemblies that is capable of enhancing the mass spectrometry-based detection of peptides and proteins in human breast milk.

Combinatorial Electrophoresis and Mass Spectrometry-Based Proteomics in Breast Milk for Breast Cancer Biomarker Discovery.

Innovations in approaches for early detection and individual risk assessment of different cancers, including breast cancer (BC), are needed to reduce cancer morbidity and associated mortality. The assessment of potential cancer biomarkers in accessible bodily fluids provides a novel approach to identify the risk and/or onset of cancer. Biomarkers are biomolecules, such as proteins, that are indicative of an abnormality or a disease.

Surfaces that Adhesively Discriminate Breast Epithelial Cell Lines and Lymphocytes in Buffer and Human Breast Milk.

We report new surface coatings that adhesively distinguish three breast epithelial cell lines (MCF-10A, MCF-7, and TMX2-28) when cell suspensions in buffer or breast milk are flowed over the coatings. We also report the selective capture of epithelial cells and rejection of Jurkat lymphocytes, with average selectivities exceeding 60 and captured cell purities often exceeding >99%. The surfaces achieve the dual goals of selective cell capture and resistance to fouling by proteins and other components of breast milk.

DNA methylation in breast cancers: Differences based on estrogen receptor status and recurrence.

DNA methylation plays a role in the etiology of primary breast cancers. We analyzed paired primary and second breast tumors to elucidate the role of methylation in recurrence. Methylation profiles from paired primary and second breast tumors of 23 women were assessed using the HumanMethylation450 BeadChip.

Dietary Intervention to Increase Fruit and Vegetable Consumption in Breastfeeding Women: A Pilot Randomized Trial Measuring Inflammatory Markers in Breast Milk.

Background: Diets rich in fruits and vegetables (F/V) can reduce the inflammatory profile of circulating cytokines and potentially decrease the risk of breast cancer. However, the extent to which a diet rich in F/V alters cytokine levels in breast tissue remains largely unknown. Breast milk provides a means of assessing concentrations of secreted cytokines in the breast microenvironment and is a potential tool for studying the effects of diet on inflammation in breast tissue and breast cancer risk.

Pro-inflammatory cytokines and growth factors in human milk: an exploratory analysis of racial differences to inform breast cancer etiology.

Background: Analysis of cytokines and growth factors in human milk offers a noninvasive approach for studying the microenvironment of the postpartum breast, which may better reflect tissue levels than testing blood samples. Given that Black women have a higher incidence of early-onset breast cancers than White women, we hypothesized that milk of the former contains higher levels of pro-inflammatory cytokines, adipokines, and growth factors.

Methods: Participants included 130 Black and 162 White women without a history of a breast biopsy who completed a health assessment questionnaire and donated milk for research.

TROP2 methylation and expression in tamoxifen-resistant breast cancer.

Background: The DNA methyltransferase 1 inhibitor, 5-Aza-2'-deoxycytidine (5-Aza-dC) is a potential treatment for breast cancer. However, not all breast tumors will respond similarly to treatment with 5-Aza-dC, and little is known regarding the response of hormone-resistant breast cancers to 5-Aza-dC.

Methods: We demonstrate that 5-Aza-dC-treatment has a stronger effect on an estrogen receptor-negative, Tamoxifen-selected cell line, TMX2-28, than on the estrogen receptor-positive, MCF7, parental cell line.

Comparative two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) of human milk to identify dysregulated proteins in breast cancer.

Breast cancer (BC) remains a major cause of mortality, and early detection is considered important for reducing BC-associated deaths. Early detection of BC is challenging in young women, due to the limitations of mammography on the dense breast tissue of young women. We recently reported results of a pilot proteomics study, using one-dimensional polyacrylamide gel electrophoresis (1D-PAGE) and mass spectrometry (MS) to investigate differences in milk proteins from women with and without BC.