Kathleen F. Arcaro's research while affiliated with University of Massachusetts Amherst and other places
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Publications (113)
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 as important for early diagnosis and prediction of the cancer risk. Protein biomarkers could be investigated by large-scale protein investigation or proteomics, u...
While it is widely recognized that nutrition during pregnancy and lactation can affect the microbiome of breast milk as well as the formation of the infant gut microbiome, we are only just beginning to understand the extent to which maternal diet impacts these microbiomes. Given the importance of the microbiome for infant health, we conducted a com...
Objective
The inflammatory signature of human milk is an indicator of mammary gland health and has implications for infant nutrition, growth, and immune system development. We hypothesized that measurement of mammary epithelium permeability would provide important context for the interpretation of the inflammatory signature of human milk.
Methods...
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...
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 emph...
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-te...
Breast cancer (BC), one of the most common cancers, is a leading cause of death for women in the United States. An estimated 1 in 8 women in the United States will develop BC in their lifetime. Early diagnosis and treatment of BC is crucial, and protein biomarkers for this disease could make this possible. Mass spectrometry (MS)-based proteomic met...
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...
Objective: To evaluate the immune response to COVID-19 mRNA-based vaccines present in breastmilk and the transfer of the immune response to the breastfeeding child.
Methods: A prospective cohort study enrolled 30 lactating women who received an mRNA-based COVID-19 vaccine between January and April 2021. Women provided serial milk samples, which inc...
Objective: 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.
Methods: 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 posi...
Background:
White blood cell (WBC) DNA may be associated with 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 non-ca...
Background: Colostrum provides an immune sharing between a mother and her infant. The transfer in colostrum of antibodies against SARS-CoV-2 and the elicited cytokines may provide crucial protection to the infant. There is limited literature on the immune response to SARS-CoV-2 present in colostrum.
Objective: To evaluate the presence of antibodies...
Background: Colostrum provides an immune sharing between a mother and her infant. The transfer in colostrum of antibodies against SARS-CoV-2 and the elicited cytokines may provide crucial protection to the infant. There is limited literature on the immune response to SARS-CoV-2 present in colostrum. Objective: To evaluate the presence of antibodies...
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, hi...
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. Our objective was to determine individual...
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 mi...
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 i...
Black women in the U.S. are disproportionately affected by early-onset, triple-negative breast cancer. DNA methylation has shown differences by race in healthy and tumor breast tissues. We examined associations between genome-wide DNA methylation levels in breast milk and breast cancer risk factors, including race, to explain how this reproductive...
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 a...
Background: Emerging work has demonstrated that histologically normal (non-tumor) tissue adjacent to breast tumor tissue shows evidence of molecular alterations related to tumorigenesis, referred to as field cancerization effects. Although changes in DNA methylation are known to occur early in breast carcinogenesis and the landscape of breast tumor...
Background: 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...
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 ce...
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 t...
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. Twelve women had estrogen receptor positiv...
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...
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 h...
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 po...
Introduction: Identifying biomarkers of breast cancer risk among young women would have value in developing effective screening and prevention strategies at early ages. We have proposed that DNA methylation analysis of breast milk may provide breast cancer risk information among young women, and could possibly provide etiologic clues related to the...
Detection of breast cancer (BC) in young women is challenging because mammography, the most common tool for detecting BC, is not effective on the dense breast tissue characteristic of young women. In addition to the limited means for detecting their BC, young women face a transient increased risk of pregnancy-associated BC. As a consequence, reprod...
Background
Several studies have suggested that global DNA methylation in circulating white blood cells (WBC) is associated with breast cancer risk.
Methods
To address conflicting results and concerns that the findings for WBC DNA methylation in some prior studies may reflect disease effects, we evaluated the relationship between global levels of W...
The egg yolk precursor protein vitellogenin is widely used as a biomarker of estrogen exposure in male fish. However, standardized methodology is lacking and little is known regarding the reproducibility of results among laboratories using different equipment, reagents, protocols, and employing different data analysis programs. To address this data...
It is not yet clear whether white blood cell DNA global methylation is associated with breast cancer risk. In this review we examine the relationships between multiple breast cancer risk factors and three markers of global DNA methylation: LINE-1 , 5-mdC, and Alu . A literature search was conducted using Pubmed up to April 1, 2016, using combinatio...
Prior candidate gene studies have shown that methylation-induced silencing of tumor suppressor genes in breast milk is 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-wi...
This work explored how molecularly non-specific polycationic nanoscale features on a collecting surface control kinetic and selectivity aspects of mammalian cell capture. Key principles for selective collector design were demonstrated by comparing the capture of two closely related breast cancer cell lines: MCF-7 and TMX2-28. TMX2-28 is a tamoxifen...
Introduction: Giving birth may be associated with a transient increase in breast cancer risk post-delivery and with elevated risk of basal breast cancers, especially in the absence of breastfeeding, whereas parity is related to lower risk of postmenopausal ER-positive tumors. Black women develop more early-onset and basal breast cancers than White...
This review summarizes methods related to the study of human breastmilk in etiologic and biomarkers research. Despite the importance of reproductive factors in breast carcinogenesis, factors that act early in life are difficult to study because young women rarely require breast imaging or biopsy, and analysis of critical circulating factors (e.g.,...
Background:
Most women with primary breast cancers that express estrogen receptor alpha (ER or ESR1) are treated with endocrine therapies including the anti-estrogen tamoxifen, but resistance to these anti-endocrine therapies often develops. This study characterizes the expression of hormone receptors, and the mRNA and DNA methylation levels of do...
Background:
Whether depression and antidepressant (AD) use might influence breast cancer risk is unclear, and these exposures have not been evaluated together in a single, prospective cohort study of breast cancer risk.
Methods:
Among 71,439 postmenopausal women in the Women's Health Initiative Observational Study (WHI-OS), we estimated multivar...
Epigenetics is a field of study that invites an interdisciplinary interaction of the social and biological sciences. This collaboration has, in fact, led to a blossoming research community over the past two decades, which is using new data, methods, and conceptual frameworks to address a host of old and emergent research questions. A recent (2014)...
Resistance to radiation therapy constitutes a significant challenge in the treatment of head and neck squamous cell cancer (HNSCC). Alteration in DNA methylation is thought to play a role in this resistance. Here, we analyzed DNA methylation changes in a matched model of radiation resistance for HNSCC using the Illumina HumanMethylation450 BeadChip...
TGF-β plays a dual role in breast carcinogenesis, acting at early stages as tumor-suppressors and later as tumor-promoters. TGF-β isoforms are expressed in breast tissues and secreted in milk, suggesting that analysis of levels in milk might be informative for breast cancer risk. Accordingly, we assessed TGF-β2 levels in milk from women who had und...
Experimental and epidemiologic data support a protective role for melatonin in breast cancer etiology, yet studies in premenopausal women are scarce. In a case-control study nested within the Nurses' Health Study II cohort, we measured the concentration of melatonin's major urinary metabolite, 6-sulfatoxymelatonin (aMT6s), in urine samples collecte...
Background:
Chlamydia trachomatis (C. trachomatis) is a clinically significant human pathogen and one of the leading causative agents of sexually transmitted diseases. As obligate intracellular bacteria, C. trachomatis has evolved strategies to redirect the host's signaling and resources for its own survival and propagation. Despite the clinical n...
Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA
Women who receive adjuvant tamoxifen for estrogen receptor (ER) positive breast cancer may develop drug resistant tumors through several pathways. DNA methylation of CpG islands in gene promoters is a mechanism of gene silencing, which has been implicated in acquired tamoxifen r...
S-phase kinase-associated protein 2 (SKP2) is an important cell cycle regulator, targeting the cyclin-dependent kinase (CDK) inhibitor p27 for degradation, and is frequently overexpressed in breast cancer. p27 regulates G1/S transition by abrogating the activity of cyclin/CDK complexes. p27 can undergo phosphorylation at serine 10 (pSer10p27). This...
Background:
Breast cancer is the most frequently diagnosed cancer among Turkish women and both the incidence and associated mortality appear to be increasing. Of particular concern is the percentage of young women diagnosed with breast cancer; roughly 20% of all breast cancer diagnoses in Turkey are in women younger than 40 years. Increased DNA me...
Although mammography and treatment advances have led to declines in breast cancer mortality in the United States, breast cancer remains a major cause of morbidity and mortality. Breast cancer in young women is associated with increased mortality and current methods of detecting breast cancers in this group of women have known limitations. Tools for...
Background
Retroviral sequences 90-95% homologous to the mouse mammary tumor virus (MMTV) were present in 38% of the breast cancers studied from American women and were not detectable in non-tumor breast tissue from the same patient. The entire proviral structure was described and viral particles were isolated from primary cultures of human breast...
Bisphenol A (BPA) is a synthetic compound with structural similarities to the hormone 17β-estradiol. BPA is a major component of polycarbonate plastics and epoxy resins, which are used in the production of plastic containers, metal can linings, dental sealants, thermal receipt paper and household paper products. Incomplete polymerization of BPA as...
Background:
The extent to which white blood cell (WBC) DNA methylation provides information on the status of breast epithelial cell DNA is unknown.
Patients and methods:
We examined the correlation between methylation in Ras-association domain family-1 gene (RASSF1), a tumor-suppressor gene, and methylation in repetitive elements in paired sets...
Roughly two-thirds of all breast cancers are ERα-positive and can be treated with the antiestrogen, Tamoxifen, however resistance occurs in 33% of women who take the drug for more than 5 y. Aberrant DNA methylation, an epigenetic mechanism that alters gene expression in cancer, is thought to play a role in this resistance. To develop an understandi...
Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC
Epidemiological data indicate that dietary consumption of cruciferous vegetables may reduce the risk of many cancers including breast cancer. Cruciferous vegetables contain high levels of glucosinolates; stable phytochemicals that when metabolized produce cancer-preventing...
Current models of assessing breast cancer risk do not adequately predict whether an individual woman will develop breast cancer. Assessment of healthy tissue for epigenetic changes that result in silencing of tumor suppressor genes may provide a more accurate assessment of individual breast cancer risk. Breast milk is an underutilized source of epi...
Estrogen receptor (ER) status remains one of the most important breast cancer diagnostic and prognostic biomarkers. Roughly two-thirds of all breast cancers are ER-positive and can be treated with the anti-estrogen, Tamoxifen, however resistance occurs in 33% of women who take the drug for more than 5 years.
MCF-7 breast cancer cells were previousl...
The pregnancy–lactation cycle (PLC) is a period in which the breast is transformed from a less-developed, nonfunctional organ
into a mature, milk-producing gland that has evolved to meet the nutritional, developmental, and immune protection needs of
the newborn. Cessation of lactation initiates a process whereby the breast reverts to a resting stat...
Breast cancer is a heterogeneous disease that varies in its biology and response to therapy. A foremost threat to patients is tumor invasion and metastasis, with the greatest risk among patients diagnosed with triple-negative and/or basal-like breast cancers. A greater understanding of the molecular mechanisms underlying cancer cell spreading is ne...
Tumors are capable of shedding DNA into the blood stream. This shed DNA may be recovered from serum or plasma. The objective of this study was to evaluate whether pyrosequencing promoter DNA in a panel of 12 breast cancer-related genes (APC, BRCA1, CCND2, CDH1, ESR1, GSTP1, HIN1, P16, RARβ, RASSF1, SFRP1 and TWIST) to measure the degree of methylat...
Background:
Breast cancer risk increases during pregnancy and remains elevated for a number of years thereafter. Cancer-associated proteins that are secreted into breast milk may provide a means to detect cancer in the lactating breast or to assess future breast cancer risk.
Objective:
To determine whether proteins linked to breast cancer would...
Background
Paralemmin-1 is a phosphoprotein lipid-anchored to the cytoplasmic face of membranes where it functions in membrane dynamics, maintenance of cell shape, and process formation. Expression of paralemmin-1 and its major splice variant (Δ exon 8) as well as the extent of posttranslational modifications are tissue- and development-specific. P...
First full term pregnancy (FFTP) completed at a young age has been linked to low long term breast cancer risk, whereas late FFTP pregnancy age confers high long term risk, compared to nulliparity. Our hypothesis was that proteins linked to breast cancer would be differentially expressed in human milk collected at three time points during lactation...
Accurately identifying women at increased risk of developing breast cancer will provide greater opportunity for early detection and prevention. DNA promoter methylation is a promising biomarker for assessing breast cancer risk. Breast milk contains large numbers of exfoliated epithelial cells that are ideal for methylation analyses. Exfoliated epit...
Gene specific promoter methylation in breast epithelial cells is considered one of the most promising biomarkers for assessing breast cancer risk. Unfortunately, obtaining breast epithelial cells is difficult. We recently demonstrated that human breast milk provides a source of epithelial cells useful for assessing breast cancer risk through analys...
Background: Changes in DNA methylation patterns are a common feature of malignant cells. Methylation is an epigenetic change that affects gene expression. Methylation of a cytosine guanine dinucleotide-rich area (CpG island) of the promoter region of a gene that is normally unmethylated is correlated with silencing of that gene. Certain tumor suppr...
Breast cancer is the second most commonly diagnosed cancer among women, and is difficult to diagnose during pregnancy and lactation. Frequent methylation of the promoter region of key tumor suppressor genes occurs in the early etiology of breast cancer. We aimed to evaluate the feasibility of using DNA extracted from the epithelial cells exfoliated...