Recent cbcrp_rw items

Electroacupuncture improves cognitive function and neuropsychiatric symptoms in breast cancer survivors: a pilot randomized controlled trial

Fri, 24 Apr 2026 00:00:00 +0000

BACKGROUND: We conducted a randomized, double-blinded pilot trial to compare the impact of two electroacupuncture (EA) regimens on co-occurring neuropsychiatric symptoms among breast cancer survivors (BCS). METHODS: BCS who self-reported cognitive impairment, fatigue, insomnia, or psychological distress were randomized (1:1) to receive ten weekly EA to target either neuropsychiatric-specific (nEA) or non-neuropsychiatric-specific (sEA) acupoints. Primary endpoints were the within-group pre-post effect sizes (Glass's Δ) in symptom severities, adjusted for multiple comparisons (p-adjusted). Outcomes were assessed using neurocognitive tests (CANTAB®), PROs (FACT-Cog, MFSI-SF, EORTC QLQ-C30), plasma biomarkers, and neuroimaging. Responders were defined by reliable change index (for objective cognition) or MCID (for PROs). RESULTS: Thirty-five were recruited, with 30 (86%) completing all sessions. The mean (±SD) age was 58.2 (±12.2) years, and 86% reported co-occurring symptoms. Following...

CDCP1/mitochondrial Src axis increases electron transport chain function to promote metastasis in triple-negative breast cancer

Wed, 1 Oct 2025 00:00:00 +0000

BackgroundTriple-negative type of breast cancer (TNBC) has limited therapeutic options and frequently metastasizes, leading to low survival rates. Oxidative phosphorylation (OXPHOS) is a driver of TNBC metastasis, but the signaling underlying this metabolic change is poorly understood.MethodsWe performed metabolic assays and assessed migratory and metastatic potential in cells with manipulated CDCP1/mitochondrial Src signaling.ResultsWe show that the pro-metastatic cell surface protein CUB-domain containing protein 1 (CDCP1) activates Src kinase localized in mitochondria, which potently induces OXPHOS and TNBC migration. Genetic targeting of either CDCP1 or mitochondrial Src, as well as pharmacological inhibition of Src reduce OXPHOS in vitro. We further show that mitochondrial Src increases OXPHOS by stimulating Complex I activity in the electron transport chain. Importantly, rescuing Complex I activity in cells devoid of CDCP1/mitochondrial Src signaling restores both OXPHOS...

Automated Extraction of Patient-Centered Outcomes After Breast Cancer Treatment: An Open-Source Large Language Model–Based Toolkit

Fri, 12 Sep 2025 00:00:00 +0000

PURPOSE: Patient-centered outcomes (PCOs) are pivotal in cancer treatment, as they directly reflect patients' quality of life. Although multiple studies suggest that factors affecting breast cancer-related morbidity and survival are influenced by treatment side effects and adherence to long-term treatment, such data are generally only available on a smaller scale or from a single center. The primary challenge with collecting these data is that the outcomes are captured as free text in clinical narratives written by clinicians. MATERIALS AND METHODS: Given the complexity of PCO documentation in these narratives, computerized methods are necessary to unlock the wealth of information buried in unstructured text notes that often document PCOs. Inspired by the success of large language models (LLMs), we examined the adaptability of three LLMs, GPT-2, BioGPT, and PMC-LLaMA, on PCO tasks across three institutions, Mayo Clinic, Emory University Hospital, and Stanford University. We developed...

Determination of Hormonal Growth Promotants in Beef Using Liquid Chromatography–Tandem Mass Spectrometry

Mon, 11 Aug 2025 00:00:00 +0000

Hormonal growth promotants (HGPs) are a class of pharmaceutical agents commonly administered to cattle in the United States to improve growth rates of the animal, alter behavior, or to improve the desired characteristics of retail cuts of meat. There is a concern that low residual concentrations of HGPs may remain in tissue after slaughter, and consumption of tissues containing these compounds may increase the risk of adverse health outcomes, including cancer. Sensitive and selective methods are necessary to assess exposure of HGPs by populations that consume meat products from animals that may have been administered HGPs. A liquid chromatography-tandem mass spectrometry method was developed and validated to detect the low-level presence of HGPs including estradiol, testosterone, estradiol benzoate, melengestrol, melengestrol acetate, progesterone, testosterone propionate, trenbolone, trenbolone acetate, and α-zearalanol in retail cuts of meat following a liquid-liquid extraction...

Estimated human intake of endogenous and exogenous hormones from beef in the United States

Mon, 11 Aug 2025 00:00:00 +0000

BackgroundEndogenous and exogenous hormones may be present in beef. Human consumption of hormones has been linked to adverse health effects.ObjectiveTo estimate daily intake of hormonal growth promotants (HGP) from beef consumed by the US population.MethodsWe combined self-reported beef consumption information from a nationally-representative survey with concentrations of 12 HGP measured in 397 samples of retail beef/fat purchased in California. We defined typical, high, and maximum intake scenarios assuming self-reported consumed beef contained the mean, 95th percentile, and maximum concentrations of each HGP, respectively. We estimated distributions of usual (i.e., long-term) daily intake and short-term daily intake (µg/kg/day). We calculated the hazard quotient (HQ), or ratio of estimated intake to the World Health Organization’s acceptable daily intake (ADI) for the HGP.ResultsThe highest estimated HQs were found for melengestrol acetate (MGA). For usual daily intake under...

A dataset of chronic nicotine-induced genes in breast cancer cells

Thu, 22 May 2025 00:00:00 +0000

These data show the differentially expressed genes (DEG) from HCC38 breast cancer cell line chronically exposed to nicotine versus vehicle control. Additional data is also provided from dynamic trajectory analysis, identifying the most dynamic genes due to chronic nicotine treatment. To produce this dataset, we first performed single cell RNA sequencing from HCC38 cells chronically treated with vehicle or nicotine, followed by scanpy analysis to yield 6 discrete cell clusters at conservative resolution. We then evaluated differential gene expression between chronic nicotine and control cells for each individual cluster or in the whole sample using PyDESeq2. For dynamic trajectory analysis, Velocyto (0.6) was used to estimate the spliced and unspliced counts for each gene between chronic nicotine-treated cells and vehicle, allowing computation of gene velocities. These data are useful for analysing the expression of individual genes or gene velocities either in the whole sample...

Cover Feature: Sustainability‐Driven Accelerated Shear‐Mediated Immunoassay for Amyotrophic Lateral Sclerosis Detection (ChemSusChem 21/2024)

Fri, 25 Apr 2025 00:00:00 +0000

The Cover Feature shows plasticware for biomarker measurement, which constitutes a notable portion of the plastic waste stream from medical consumables. We have developed a portable vortex fluidic device (P‐VFD) with a membrane array to initiate fast reaction, detection and analysis of a clinically relevant protein biomarker, p75ECD. It shows significant potential to replace traditional assay plates with a membrane, providing a greener and more sustainable alternative in biofluid biomarker measurement. More information can be found in the Research Article by X. Luo, M.‐L. Rogers, C. L. Raston and co‐workers.

Comprehensive Nontargeted Analysis of Drinking Water Supplies to Identify Chemicals Associated with Estrogen Receptor Agonism or Present in Regions of Elevated Breast Cancer Occurrence

Thu, 3 Apr 2025 00:00:00 +0000

To explore the hypothesis that differential exposures to estrogen active chemicals may contribute to regional disparities in cancer incidence, a comprehensive targeted and nontargeted analysis was conducted over two seasons (2020) for drinking water samples from 120 households served by 8 public water systems (4 with historically elevated breast cancer incidence) and from 15 brands of retail water. All samples were analyzed using gas and liquid chromatography with high-resolution mass spectrometry and a bioassay for estrogen receptor agonism. Target compounds included disinfection byproducts, per- and polyfluoroalkyl substances (PFAS), trace elements, and compounds selected for their possible relation to breast cancer. Over 7500 GC and LC nontargeted molecular features passed all quality control filters in each sampling season and were prioritized for identification if they were related to measured estrogen receptor agonism or were present at higher levels in areas with high breast...

Folate Deficiency Inhibits Development of the Mammary Gland and its Associated Lymphatics in FVB Mice

Tue, 1 Apr 2025 00:00:00 +0000

BACKGROUND: Folate is essential for DNA synthesis, DNA repair, cell proliferation, development, and morphogenesis. Folic acid (FA) is a nutritional supplement used to fortify human diets. OBJECTIVES: We investigated the effects of dietary FA on early mammary gland (MG) development and hyperplasia. METHODS: Study 1: nulliparous female FVB wild-type (WT) mice were fed control (Con; 2 mg FA/kg), deficient (Def; 0 mg FA/kg), excess (Ex; 5 mg FA/kg), or super excess (S-Ex; 20 mg FA/kg) diets for 8 wk before mating to WT or heterozygous FVB/N-Tg[mouse mammary tumor virus long terminal repeat (MMTV)-polyomavirus middle T antigen (PyVT)]634Mul/J (MMTV-PyMT+/-) transgenic males. Dams were fed these diets until they weaned WT or MMTV-PyMT+/- pups, which were fed the dam's diet from postnatal day (PND) 21 to 42. Tissues were collected from female progeny at PNDs 1, 21, and 42. Study 2: Con or Def diets were fed to WT intact females and males from PND 21 to 56, or to ovariectomized...

Material hardship, forced displacement, and negative health outcomes among unhoused people who use drugs in Los Angeles, California and Denver, Colorado: a latent class analysis

Sun, 2 Mar 2025 00:00:00 +0000

BackgroundHomelessness is a growing concern in the United States, especially among people who use drugs (PWUD). The degree of material hardship among this population may be linked to worse health outcomes. PWUD experiencing homelessness in urban areas are increasingly subjected to policies and social treatment, such as forced displacement, which may worsen material hardship. It is critical to describe hardship among PWUD and examine if it is linked to health outcomes.MethodsData were collected as part of a prospective cohort study of PWUD in Los Angeles, California and Denver, Colorado (n = 476). Analysis sample size was smaller (N = 395) after selecting for people experiencing homelessness and for whom data were complete. Five indicators assessing hardship (difficulty finding food, clothing, restrooms, places to wash/shower, and shelter) in the past three months were obtained from participants at baseline and were used in latent class analysis (LCA). We chose a base latent class...

S100A8/A9 innate immune signaling as a distinct mechanism driving progression of smoking-related breast cancers

Thu, 30 Jan 2025 00:00:00 +0000

Smoking plays an underappreciated role in breast cancer progression, increasing recurrence and mortality in patients. Here, we show that S100A8/A9 innate immune signaling is a molecular mechanism that identifies smoking-related breast cancers and underlies their enhanced malignancy. In contrast to acute exposure, chronic nicotine increased tumorigenicity and reprogrammed breast cancer cells to express innate immune response genes. This required the α7 nicotinic acetylcholine receptor, which elicited dynamic changes in cell differentiation, proliferation, and expression of secreted cytokines, such as S100A8 and S100A9, as assessed by unbiased scRNA-seq. Indeed, pharmacologic or genetic inhibition of S100A8/A9-RAGE receptor signaling blocked nicotine’s tumor-promoting effects. We also discovered Syntaphilin (SNPH) as an S100A8/A9-dependent gene enriched specifically in estrogen receptor-negative (ER-) cancers from former smokers, linking this response to patient disease. Together,...

A hybrid epithelial-mesenchymal transition program enables basal epithelial cells to bypass stress-induced stasis and contributes to a metaplastic breast cancer progenitor state

Fri, 3 Jan 2025 00:00:00 +0000

BackgroundHuman mammary epithelial cell (HMEC) cultures encounter a stress-associated barrier termed stasis, during which most cells adopt a senescence-like phenotype. From these cultures, rare variants emerge from the basal epithelial population, re-initiating growth. Variants exhibit pre-malignant properties, including an aberrant epigenetic program that enables continued proliferation and acquisition of genetic changes. Following oncogenic transformation, variants produce tumors that recapitulate the histopathological characteristics of metaplastic breast cancer (MBC), a rare and aggressive subtype marked by the differentiation of neoplastic epithelium into squamous and mesenchymal elements.MethodsUsing a serum-free HMEC culture system, we probed the capacity for phenotypic plasticity inherent to basal epithelial cell populations from human breast tissue as they navigated stasis and emerged as variant populations.ResultsWe observed robust activation of a TGF-β-dependent...

Organophosphate pesticide exposure and risk of SARS-CoV-2 infection

Tue, 17 Dec 2024 00:00:00 +0000

Several studies have reported immune modulation by organophosphate (OP) pesticides, but the relationship between OP exposure and SARS-CoV-2 infection is yet to be studied. We used two different measures of OP pesticide exposure (urinary biomarkers (N = 154) and residential proximity to OP applications (N = 292)) to examine the association of early-childhood and lifetime exposure to OPs and risk of infection of SARS-CoV-2 using antibody data. Our study population consisted of young adults (ages 18-21 years) from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) Study, a longitudinal cohort of families from a California agricultural region. Urinary biomarkers reflected exposure from in utero to age 5 years. Residential proximity reflected exposures between in utero and age 16 years. SARS-CoV-2 antibodies in blood samples collected between June 2022 and January 2023 were detected via two enzyme linked immunosorbent assays, each...

Trends in NHANES Biomonitored Exposures in California and the United States following Enactment of California’s Proposition 65

Wed, 20 Nov 2024 00:00:00 +0000

BACKGROUND: The prevalence of toxic chemicals in US commerce has prompted some states to adopt laws to reduce exposure. One with broad reach is California's Proposition 65 (Prop 65), which established a list of chemicals that cause cancer, developmental harm, or reproductive toxicity. The law is intended to discourage businesses from using these chemicals and to minimize consumer exposure. However, a key question remains unanswered: Has Prop 65 reduced population-level exposure to the listed chemicals? OBJECTIVE: We used national biomonitoring data from the Centers for Disease Control and Prevention (CDC) to evaluate the impact of Prop 65 on population-level exposures. METHODS: We evaluated changes in blood and urine concentrations of 37 chemicals (including phthalates, phenols, VOCs, metals, PAHs, and PFAS), among US National Health and Nutrition Examination Survey (NHANES) participants in relation to the time of chemicals' Prop 65 listing. Of these, 11 were listed prior to,...

Breast Cancer-Related Chemical Exposures in Firefighters

Sat, 2 Nov 2024 00:00:00 +0000

To fill a research gap on firefighter exposures and breast cancer risk, and guide exposure reduction, we aimed to identify firefighter occupational exposures linked to breast cancer. We conducted a systematic search and review to identify firefighter chemical exposures and then identified the subset that was associated with breast cancer. To do this, we compared the firefighter exposures with chemicals that have been shown to increase breast cancer risk in epidemiological studies or increase mammary gland tumors in experimental toxicology studies. For each exposure, we assigned a strength of evidence for the association with firefighter occupation and for the association with breast cancer risk. We identified twelve chemicals or chemical groups that were both linked to breast cancer and were firefighter occupational exposures, including polycyclic aromatic hydrocarbons, volatile aromatics, per- and polyfluoroalkyl substances, persistent organohalogens, and halogenated organophosphate...

Mixed contaminant exposure in tapwater and the potential implications for human-health in disadvantaged communities in California

Thu, 3 Oct 2024 00:00:00 +0000

Water is an increasingly precious resource in California as years of drought, climate change, pollution, as well as an expanding population have all stressed the state's drinking water supplies. Currently, there are increasing concerns about whether regulated and unregulated contaminants in drinking water are linked to a variety of human-health outcomes particularly in socially disadvantaged communities with a history of health risks. To begin to address this data gap by broadly assessing contaminant mixture exposures, the current study was designed to collect tapwater samples from communities in Gold Country, the San Francisco Bay Area, two regions of the Central Valley (Merced/Fresno and Kern counties), and southeast Los Angeles for 251 organic chemicals and 32 inorganic constituents. Sampling prioritized low-income areas with suspected water quality challenges and elevated breast cancer rates. Results indicated that mixtures of regulated and unregulated contaminants were observed...

Chromosomal instability as an architect of the cancer stemness landscape

Thu, 3 Oct 2024 00:00:00 +0000

Despite a critical role for tumor-initiating cancer stem cells (CSCs) in breast cancer progression, major questions remain about the properties and signaling pathways essential for their function. Recent discoveries highlighting mechanisms of CSC-resistance to the stress caused by chromosomal instability (CIN) may provide valuable new insight into the underlying forces driving stemness properties. While stress tolerance is a well-known attribute of CSCs, CIN-induced stress is distinctive since levels appear to increase during tumor initiation and metastasis. These dynamic changes in CIN levels may serve as a barrier constraining the effects of non-CSCs and shaping the stemness landscape during the early stages of disease progression. In contrast to most other stresses, CIN can also paradoxically activate pro-tumorigenic antiviral signaling. Though seemingly contradictory, this may indicate that mechanisms of CIN tolerance and pro-tumorigenic inflammatory signaling closely collaborate...

Per- and polyfluoroalkyl substances (PFAS) in drinking water in Southeast Los Angeles: Industrial legacy and environmental justice

Fri, 13 Sep 2024 00:00:00 +0000

Per- and polyfluoroalkyl substances (PFAS) are persistent chemicals of increasing concern to human health. PFAS contamination in water systems has been linked to a variety of sources including hydrocarbon fire suppression activities, industrial and military land uses, agricultural applications of biosolids, and consumer products. To assess PFAS in California tap water, we collected 60 water samples from inside homes in four different geographic regions, both urban and rural. We selected mostly small water systems with known history of industrial chemical or pesticide contamination and that served socioeconomically disadvantaged communities. Thirty percent of the tap water samples (18) had a detection of at least one of the 32 targeted PFAS and most detections (89 %) occurred in heavily industrialized Southeast Los Angeles (SELA). The residents of SELA are predominately Latino and low-income. Concentrations of perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid...

Optimizing Continuous‐Flow Biocatalysis with 3D‐Printing and Inline IR Monitoring

Thu, 29 Aug 2024 00:00:00 +0000

Abstract Enzymatic biocatalysis typically generates less waste, uses less water, and minimizes energy consumption compared to traditional chemical methods. Efficient, cell‐free biosynthesis relies on the reuse of its valuable biocatalysts. Immobilization of enzymes on solid supports, such as enzyme carrier resins (ECRs), offers a reliable and widely deployed approach to maximize enzyme turnover in cell‐free biosynthesis. We focus on two major bottlenecks associated with optimizing cell‐free biocatalysis. First, we apply our lab's 3D‐printed labware to screen ECRs in 96‐well mini‐reactors to optimize enzyme immobilization conditions. Second, we introduce inline infrared spectroscopy to monitor bioreactor output and maximize enzyme productivity. Urease provides a model system for examining immobilization conditions and continuous assessment of biocatalyst performance. As required for the high substrate concentrations to improve process efficiency and minimize waste, urease was...

Disinfection Byproducts in Drinking Water from the Tap: Variability in Household Calculated Additive Toxicity (CAT)

Tue, 27 Aug 2024 00:00:00 +0000

Recent studies have implemented a calculated additive toxicity (CAT) approach that sums measured disinfection byproduct (DBP) concentrations weighted by their respective in vitro bioassay potencies to estimate their associated risk in disinfected waters. In this study, the CAT approach was used to systematically investigate 21 regulated and unregulated DBPs measured in drinking water at the household level. Water samples from the tap were collected from over 120 randomly selected participants supplied by eight public water systems using four distinct source water types, two types of disinfection processes, and across two seasons. The purpose of this study was to compare CAT using multiple biological end points, examine household variability, identify DBPs driving toxicity, and assess if current regulated DBPs are adequate predictors of unregulated DBPs. Our results support the significance of unregulated DBPs, particularly haloacetonitriles and iodoacetic acid, as drivers of toxicity....

Exposure to outdoor ambient air toxics and risk of breast cancer: The multiethnic cohort

Thu, 11 Apr 2024 00:00:00 +0000

BACKGROUND: A growing literature has reported associations between traffic-related air pollution and breast cancer, however there are fewer investigations into specific ambient agents and any putative risk of breast cancer development, particularly studies occurring in populations residing in higher pollution areas such as Los Angeles. OBJECTIVES: To estimate breast cancer risks related to ambient air toxics exposure at residential addresses. METHODS: We examined the relationships between ambient air toxics and breast cancer risk in the Multiethnic Cohort among 48,665 California female participants followed for cancer from 2003 through 2013. We obtained exposure data on chemicals acting as endocrine disruptors or mammary gland carcinogens from the National-Scale Air Toxics Assessment. Cox proportional hazards models were used to estimate breast cancer risk per one interquartile range (IQR) increase in air toxics exposure lagged by 5-years. Stratified analyses were conducted by...

Plasma glucocorticogenic activity, race/ethnicity and alcohol intake among San Francisco Bay Area women

Mon, 8 Apr 2024 00:00:00 +0000

Racial and ethnic minorities are at higher risk for a variety of diseases. While sociodemographic and lifestyle factors contribute to racial/ethnic health disparities, the biological processes underlying these associations remain poorly understood. Stress and its biological consequences through the glucocorticoid receptor (GR) have been hypothesized to mediate adverse disease outcomes. In fasting morning samples of 503 control women from the San Francisco Bay Area Breast Cancer Study, we used a sensitive Chemical-Activated LUciferase gene eXpression (CALUX) assay to examine the association of sociodemographic and lifestyle factors with plasma glucocorticogenic (G) activity in three racial/ethnic groups. The G activity is a sensitive measure that reflects biological activity of total plasma glucocorticoids including cortisol and glucocorticoid-like compounds. Associations between G activity and sociodemographic and lifestyle factors were examined using multivariable linear regression...

Integrating Exposure Knowledge and Serum Suspect Screening as a New Approach to Biomonitoring: An Application in Firefighters and Office Workers

Sun, 25 Feb 2024 00:00:00 +0000

Firefighters (FF) are exposed to recognized and probable carcinogens, yet there are few studies of chemical exposures and associated health concerns in women FFs, such as breast cancer. Biomonitoring often requires a priori selection of compounds to be measured, and so, it may not detect relevant, lesser known, exposures. The Women FFs Biomonitoring Collaborative (WFBC) created a biological sample archive and conducted a general suspect screen (GSS) to address this data gap. Using liquid chromatography-quadrupole time-of-flight tandem mass spectrometry, we sought to identify candidate chemicals of interest in serum samples from 83 women FFs and 79 women office workers (OW) in San Francisco. We identified chemical peaks by matching accurate mass from serum samples against a custom chemical database of 722 slightly polar phenolic and acidic compounds, including many of relevance to firefighting or breast cancer etiology. We then selected tentatively identified chemicals for confirmation...

Examining differences in menstrual and intimate care product use by race/ethnicity and education among menstruating individuals

Tue, 6 Feb 2024 00:00:00 +0000

Introduction: United States consumers spend over two billion dollars a year on intimate care products. These products, along with scented menstrual products, are marketed for odor control, perceived "freshness," and vaginal/vulvar cleanliness. However, these scent-altering products may increase exposure to carcinogenic and endocrine-disrupting chemicals. Prior research has not adequately characterized demographic differences in product use. The objective of our study is to examine racial/ethnic and educational differences in menstrual and intimate care product use among people who menstruate. Methods: We pooled data from two US-based cross sectional studies to examine demographic characteristics and product use in 661 participants aged 18-54 years. Participants reported use of scented and unscented menstrual products (tampons, sanitary pads, and menstrual cups) and intimate care products (vaginal douches, sprays, wipes, and powders). We examined differences by race/ethnicity and...

Beauty Inside Out: Examining Beauty Product Use Among Diverse Women and Femme-Identifying Individuals in Northern Manhattan and South Bronx Through an Environmental Justice Framework

Tue, 6 Feb 2024 00:00:00 +0000

The disproportionate use of chemical straighteners and skin lighteners by women of color is a growing public health concern given the link between product use and adverse health effects. Prior studies examined product use as an individual choice but neglected social-structural factors, which influence beauty perceptions and personal decisions around product use. We used a community-based participatory research approach to characterize product use by demographics and investigated how racialized beauty norms impact use among 297 women and femme-identifying individuals in Northern Manhattan and the South Bronx. Product use varied by race/ethnicity, nativity, and messaging from family and peers. Black respondents were more likely to ever use chemical straighteners than non-Black respondents (OR = 2.0; 95% CI = 1.2-3.2), as were respondents who heard that family members express a preference for straight hair compared with respondents whose family members expressed mixed preferences...

Aprendiendo de La Vida (Learning from Life): Development of a Radionovela to Promote Preventive Health Care Utilization among Indigenous Farmworkers from Mexico Living in California

Fri, 22 Dec 2023 00:00:00 +0000

Mixtecs and Zapotecs, originating from the Oaxaca area in Mexico, are among the largest indigenous groups of workers in California. Many adults in this community only access the health care system when sick and as a last resort. This article describes the development of a radionovela to inform the community about the importance of preventive health care. It was developed following the Sabido Method. The methodology to develop a radionovela may be of interest to other public health practitioners who want to develop educational materials in an engaging format, especially for communities that rely on oral, not written information.

Loss of PPARγ activity characterizes early protumorigenic stromal reprogramming and dictates the therapeutic window of opportunity

Tue, 7 Nov 2023 00:00:00 +0000

Although robustly expressed in the disease-free (DF) breast stroma, CD36 is consistently absent from the stroma surrounding invasive breast cancers (IBCs). In this study, we primarily observed CD36 expression in adipocytes and intralobular capillaries within the DF breast. Larger vessels concentrated in interlobular regions lacked CD36 and were instead marked by the expression of CD31. When evaluated in perilesional capillaries surrounding ductal carcinoma in situ, a nonobligate IBC precursor, CD36 loss was more commonly observed in lesions associated with subsequent IBC. Peroxisome proliferator-activated receptor γ (PPARγ) governs the expression of CD36 and genes involved in differentiation, metabolism, angiogenesis, and inflammation. Coincident with CD36 loss, we observed a dramatic suppression of PPARγ and its target genes in capillary endothelial cells (ECs) and pericytes, which typically surround and support the stability of the capillary endothelium. Factors present in conditioned...

Strength of linkage disequilibrium between two vitamin D receptor markers in five ethnic groups: implications for association studies.

Wed, 1 Nov 2023 00:00:00 +0000

Markers in the 3' end of the vitamin D receptor gene have recently been associated with prostate cancer risk. To evaluate the adequacy of the commonly used BsmI restriction fragment length polymorphism as a marker of this locus, we genotyped 627 individuals from five ethnic groups for this marker, as well as for a polymorphic site in the 3' untranslated region of this gene. At the latter site, we identified 12 alleles, A13 to A24, of a poly(A) microsatellite. Allele size followed a bimodal distribution with distinct short (A13-A17) and long (A18-A24) allele populations. Poly(A) allele frequency differed by ethnicity, with the frequency of short alleles being highest in non-Hispanic whites (41%), intermediate in Hispanics and African-Americans (31 and 29%, respectively), and lowest in Japanese-Americans and Chinese (8 and 9%, respectively). In each of the ethnic groups, some degree of coupling was observed between BsmI B and short poly(A) alleles and between BsmI b and long...

Modulation of Bcl-2 protein levels by an intracellular anti-Bcl-2 single-chain antibody increases drug-induced cytotoxicity in the breast cancer cell line MCF-7.

Wed, 1 Nov 2023 00:00:00 +0000

Extensive experimental evidence suggests that Bcl-2 promotes cell survival by preventing the onset of apoptosis induced by a variety of stimuli. In addition, Bcl-2 expression has been correlated with resistance and poor response to chemotherapy in a number of cell types. Therefore, this protein represents a logical target for gene therapy strategies designed to achieve selective gene product ablation. In this study, we have developed an approach based upon intracellular expression of single-chain antibodies (sFvs) to achieve modulation of Bcl-2 protein levels in target cells. Using a transient expression system, we show that this intracellular anti-Bcl-2 sFv mediates specific reduction of Bcl-2 levels. This effect significantly enhances drug-mediated cytotoxicity in Bcl-2-overexpressing tumor cells, whereas transfection of the anti-Bcl-2 sFv did not affect the growth rate of the tumor cell lines. This method thus represents a novel and efficient way to selectively abrogate...

Analysis of Bax and Bcl-2 expression in p53-immunopositive breast cancers.

Wed, 1 Nov 2023 00:00:00 +0000

Bax and Bcl-2 are proteins that regulate programmed cell death and apoptosis. The expression of these proteins can be regulated, at least in part, by the tumor suppressor p53, but the effects of p53 are highly tissue specific. In an effort to better understand the relation between p53 and the in vivo control of the expression of Bax and Bcl-2 in adenocarcinomas of the breast, we evaluated by immunohistochemistry the expression of Bcl-2 and Bax in 149 invasive ductal carcinomas, 135 of which were chosen because of their p53 immunopositivity. The percentages of Bcl-2-immunopositive tumor cells were significantly lower in the p53-positive (median 20%) subsets as compared to the p53-negative (median 85%) subsets (P = 0. 004). Comparisons of the percentages of p53-immunopositive tumor cells with the percentages of Bcl-2- and Bax-positive cells (as continuous variables) revealed a significant inverse correlation between Bcl-2 and p53 (r = -0.41, P < 0.001) but not between Bax...

Barriers and facilitators to implementation and sustainment of guideline-recommended depression screening for patients with breast cancer in medical oncology: a qualitative study

Thu, 19 Oct 2023 00:00:00 +0000

ObjectivesImplementation of guideline-recommended depression screening in oncology presents numerous challenges. Implementation strategies that are responsive to local context may be critical elements of adoption and sustainment. We evaluated barriers and facilitators to implementation of a depression screening program for breast cancer patients in a community medical oncology setting as part of a cluster randomized controlled trial.MethodsGuided by the Consolidated Framework for Implementation Research, we employed qualitative methods to evaluate clinician, administrator, and patient perceptions of the program using semi-structured interviews. We used a team-coding approach for the data; thematic development focused on barriers and facilitators to implementation using a grounded theory approach. The codebook was refined through open discussions of subjectivity and unintentional bias, coding, and memo applications (including emergent coding), and the hierarchical structure and...

Breast cancer stem cells tolerate chromosomal instability during tumor progression via c-Jun/AXL stress signaling

Thu, 28 Sep 2023 00:00:00 +0000

Chromosomal instability (CIN) is critical for tumor evolution, yet its relationship with stemness is unclear. Here, we describe CIN as a key stress induced during tumor initiation that is uniquely tolerated by breast cancer stem cells in an activated signaling state (aCSCs). While we noted elevated CIN specifically in tumors from aCSCs, this was not intrinsic to these cells, as baseline levels were similar to non-stem cell types. This suggests that CIN is induced during tumor initiation, and that aCSCs can better tolerate this stress. Further, this increased CIN may be transient, as it was only in low-burden aCSC tumors, with levels diminishing in more established disease. Phospho-array profiling revealed specific activation of c-Jun stress signaling in aCSCs, which we hypothesized could induce genes responsible for CIN tolerance. Indeed, we identified AXL as a c-Jun dependent gene enriched in aCSCs that enhances resistance to this stress. Thus, CIN tolerance mediated by...

Translating community-based participatory research into broadscale sociopolitical change: insights from a coalition of women firefighters, scientists, and environmental health advocates

Sat, 23 Sep 2023 00:00:00 +0000

BackgroundWe report on community-based participatory research (CBPR) initiated by women firefighters in order to share successful elements that can be instructive for other community-engaged research. This CBPR initiative, known as the Women Worker Biomonitoring Collaborative (WWBC) is the first we are aware of to investigate links between occupational exposures and health outcomes, including breast cancer, for a cohort of exclusively women firefighters.MethodsIn order to be reflective of the experiences and knowledge of those most intimately involved, this article is co-authored by leaders of the research initiative. We collected leaders’ input via recorded meeting sessions, emails, and a shared online document. We also conducted interviews (N = 10) with key research participants and community leaders to include additional perspectives.ResultsFactors contributing to the initiative’s success in enacting broadscale social change and advancing scientific knowledge include (1) forming...

Efficacy of a web-based women’s health survivorship care plan for young breast cancer survivors: a randomized controlled trial

Wed, 20 Sep 2023 00:00:00 +0000

PurposeBreast cancer survivorship care plans (SCP) have limited content addressing women’s health issues. This trial tested if young breast cancer survivors who receive a web-based, women’s health SCP were more likely to improve on at least one of the four targeted issues (hot flashes, fertility-related concerns, contraception, and vaginal symptoms) compared to attention controls.MethodsA randomized controlled trial recruited female survivors ages 18–45 at diagnosis, 18–50 at enrollment, completed primary cancer treatment, and had a significant women’s health issue: moderate or higher fertility-related concerns; ≥ 4 hot flashes/day with ≥ 1 of moderate severity; ≥ 1 moderate vaginal atrophy symptoms; or not contracepting/using less effective methods. Survivors underwent stratified, block randomization with equal allocation to intervention and control groups. The intervention group accessed the online SCP; controls accessed curated resource lists. In intention-to-treat analysis,...

Design of a randomized controlled trial on the efficacy of a reproductive health survivorship care plan in young breast cancer survivors

Wed, 20 Sep 2023 00:00:00 +0000

BACKGROUND: Young breast cancer survivors (YBCS) have unmet needs for managing hot flashes, fertility-related concerns, sexual health, and contraception. PURPOSE: Describe the design and participant characteristics of a randomized controlled trial testing the efficacy of the survivorship care plan on reproductive health (SCP-R) intervention on improving hot flashes, fertility-related concerns, sexual health, and contraception in YBCS. METHODS: SCP-R is a web-based intervention with text message support encompassing evidence- based practices on four reproductive health issues. YBCS with ≥1 reproductive health issue are randomized to intervention (full SCP-R access) or attention control (access to list of online resources) arms with 24-week follow-up. The primary outcome will be improvement of at least one reproductive health issue measured by validated self-report instruments. Each YBCS nominated one healthcare provider (HCP), who can access the same materials as their patient....

A complex systems model of breast cancer etiology: The Paradigm II Model

Tue, 18 Jul 2023 00:00:00 +0000

BACKGROUND: Complex systems models of breast cancer have previously focused on prediction of prognosis and clinical events for individual women. There is a need for understanding breast cancer at the population level for public health decision-making, for identifying gaps in epidemiologic knowledge and for the education of the public as to the complexity of this most common of cancers. METHODS AND FINDINGS: We developed an agent-based model of breast cancer for the women of the state of California using data from the U.S. Census, the California Health Interview Survey, the California Cancer Registry, the National Health and Nutrition Examination Survey and the literature. The model was implemented in the Julia programming language and R computing environment. The Paradigm II model development followed a transdisciplinary process with expertise from multiple relevant disciplinary experts from genetics to epidemiology and sociology with the goal of exploring both upstream determinants...

A comprehensive preclinical study supporting clinical trial of oncolytic chimeric poxvirus CF33-hNIS-anti-PD-L1 to treat breast cancer

Fri, 7 Jul 2023 00:00:00 +0000

CF33-hNIS-anti-PD-L1 is an oncolytic chimeric poxvirus encoding two transgenes: human sodium iodide symporter and a single-chain variable fragment against PD-L1. Comprehensive preclinical pharmacology studies encompassing primary and secondary pharmacodynamics and biodistribution and safety studies were performed to support the clinical development of CF33-hNIS-anti-PD-L1. Most of the studies were performed in triple-negative breast cancer (TNBC) models, as the phase I trial is planned for patients with TNBC. Biological functions of virus-encoded transgenes were confirmed, and the virus demonstrated anti-tumor efficacy against TNBC models in mice. In a good laboratory practice (GLP) toxicology study, the virus did not produce any observable adverse effects in mice, suggesting that the doses proposed for the clinical trial should be well tolerated in patients. Furthermore, no neurotoxic effects in mice were seen following intracranial injection of the virus. Also, the risk for...

“No Place for Old Men”: Immigrant Duration, Wage Theft, and Economic Mobility among Day Laborers in Denver, Colorado

Tue, 4 Jul 2023 00:00:00 +0000

Day laborers are a highly vulnerable population, due to their contingent work arrangements, low socioeconomic position, and precarious immigration status. Earlier studies posited day labor as a temporary bridge for recent immigrants to achieve more stable employment, but recent studies have observed increasing duration of residence in the United States among foreign-born day laborers. This article draws on 170 qualitative interviews and a multi-venue, year-long street corner survey of 411 day laborers in the Denver metropolitan area to analyze how duration in the United States affects day laborers' wages, work, and wage theft experiences. Compared to recent immigrants, foreign-born day laborers with longer duration in the United States, we found, worked fewer hours and had lower total earnings but also had higher hourly wages and lower exposure to wage theft. We draw on qualitative interviews to address whether this pattern represented weathering, negative selection, or greater...

Avocado Consumption Increased Skin Elasticity and Firmness in Women ‐ A Pilot Study

Wed, 28 Jun 2023 00:00:00 +0000

BACKGROUND: Avocados are a rich dietary source of monounsaturated fatty acids, carotenoids, and phenolic compounds. Clinical studies have demonstrated that oral consumption of carotenoids improved skin aging. However, no studies have investigated whether oral intake of avocado will reduce skin aging. OBJECTIVES: We therefore performed this pilot study to assess whether oral consumption of one avocado daily for 8 weeks can reduce skin aging in healthy overweight women assessing skin physical characteristics and resistance to UVB radiation. METHODS: Thirty-nine female participants (age 27-73 years) with Fitzpatrick skin type II-IV were randomly assigned to consume either one avocado daily or continue habitual diet for 8 weeks. Facial skin elasticity, firmness, pigmentation, sebum, and hydration were determined using a cutometer on the forehead and under eye. Minimal erythema dose (MED) was determined by standardized protocol at inner arm. RESULTS: Elasticity and firmness...

Differences in personal care product use by race/ethnicity among women in California: implications for chemical exposures

Tue, 27 Jun 2023 00:00:00 +0000

BackgroundPersonal care products may contain many chemicals, some of which are suspected endocrine disrupters. This is an important source of chemical exposure for women, but little is known about how chemical exposure differs among different races/ethnicities.ObjectiveThis study examines differences in personal care product use among Black, Latina, Vietnamese, Mixed Race, and White women in California.MethodsWe used a community-based participatory process to create and administer a personal care product usage survey to 321 Black, Latina, Vietnamese, Mixed Race, and White women. We used multivariate regression models with pairwise comparisons to examine the frequency of product use by race/ethnicity.ResultsWe found distinct trends of personal care product use by race/ethnicity: Latina women typically used makeup most frequently; Black women used certain hair products or styles most frequently; and Vietnamese women were most likely to use facial cleansing products compared to other...

Risks and Opportunities to Ensure Equity in the Application of Big Data Research in Public Health

Tue, 27 Jun 2023 00:00:00 +0000

The big data revolution presents an exciting frontier to expand public health research, broadening the scope of research and increasing the precision of answers. Despite these advances, scientists must be vigilant against also advancing potential harms toward marginalized communities. In this review, we provide examples in which big data applications have (unintentionally) perpetuated discriminatory practices, while also highlighting opportunities for big data applications to advance equity in public health. Here, big data is framed in the context of the five Vs (volume, velocity, veracity, variety, and value), and we propose a sixth V, virtuosity, which incorporates equity and justice frameworks. Analytic approaches to improving equity are presented using social computational big data, fairness in machine learning algorithms, medical claims data, and data augmentation as illustrations. Throughout, we emphasize the biasing influence of data absenteeism and positionality and conclude...

Identifying Toxic Consumer Products: A Novel Data Set Reveals Air Emissions of Potent Carcinogens, Reproductive Toxicants, and Developmental Toxicants

Wed, 7 Jun 2023 00:00:00 +0000

Consumer products are important sources of exposure to harmful chemicals. Product composition is often a mystery to users, however, due to gaps in the laws governing ingredient disclosure. A unique data set that the California Air Resources Board (CARB) uses to determine how volatile organic chemicals (VOCs) from consumer products affect smog formation holds a partial solution. By analyzing CARB data on VOCs in consumer products, we identified and quantified emissions of volatile chemicals regulated under the California Safe Drinking Water and Toxic Enforcement Act ("Prop 65"). We here highlight individual chemicals as well as consumer product categories that people are likely to be exposed to as individual consumers, in the workplace, and at the population level. Of the 33 Prop 65-listed chemicals that appear in the CARB emissions inventory, we classified 18 as "top tier priorities for elimination". Among these, methylene chloride and N-methyl-2-pyrrolidone were most prevalent...

Chemotherapy-Induced Extracellular Vesicle miRNAs Promote Breast Cancer Stemness by Targeting ONECUT2

Mon, 29 May 2023 00:00:00 +0000

Cancer-secreted, extracellular vesicle (EV)-encapsulated miRNAs enable cancer cells to communicate with each other and with noncancerous cells in tumor pathogenesis and response to therapies. Here, we show that treatment with a sublethal dose of chemotherapeutic agents induces breast cancer cells to secrete EV with the capacity to stimulate a cancer stem-like cell (CSC) phenotype, rendering cancer cells resistance to therapy. Chemotherapy induced breast cancer cells to secrete multiple EV miRNAs, including miR-9-5p, miR-195-5p, and miR-203a-3p, which simultaneously targeted the transcription factor One Cut Homeobox 2 (ONECUT2), leading to induction of CSC traits and expression of stemness-associated genes, including NOTCH1, SOX9, NANOG, OCT4, and SOX2. Inhibition of these miRNAs or restoration of ONECUT2 expression abolished the CSC-stimulating effect of EV from chemotherapy-treated cancer cells. In mice bearing xenograft mammary tumors, docetaxel treatment caused...

Metabolome Wide Association Study of serum DDT and DDE in Pregnancy and Early Postpartum

Mon, 29 May 2023 00:00:00 +0000

The advancement of high-resolution metabolomics (HRM) and metabolome-wide-association study (MWAS) enables the readout of environmental effects in human specimens. We used HRM to understand DDT-induced alterations of in utero environment and potential health effects. Endogenous metabolites were measured in 397 maternal perinatal serum samples collected during 1959-1967 in the Child Health and Development Studies (CHDS) and in 16 maternal postnatal serum samples of mice treated with or without DDT. MWAS was performed to assess associations between metabolites and p,p'-DDT, o,p'-DDT and p,p'-DDE levels, followed by pathway analysis. Distinct metabolic profiles were found with p,p'-DDT and p,p'-DDE. Amino acids such arginine had a strong association with p,p'-DDT and o,p'-DDT in both women and mice, whereas lipids and acyl-carnitine intermediates were found exclusively associated with p,p'-DDE in CHDS women indicating mitochondrial impairment. It suggests that the role of serine...

Providing Health Education to Mixtec Farmworkers in California via Workshops and Radio: A Feasibility Study

Mon, 22 May 2023 00:00:00 +0000

Originating from one of the poorest areas in Mexico, Mixtecs are one of the largest indigenous groups of workers in California. Providing health education to this group is challenging because many do not speak English or Spanish, and indigenous languages are mainly oral, not written. We explored the feasibility of conveying health information through the radio and in promotora-led workshops. The study included an evaluation of the workshops through surveys before the workshop and 4 to 6 months later in a subsample of 96 indigenous women. The number of radio listeners averaged more than 2,000 per month, and 500 community members attended a workshop. Among women who completed pre- and postworkshop assessments (N = 75), there was a statistically significant increase in knowledge of how to get a wellness visit, where to get a free mammogram, and mammography screening guidelines. Women who ever had a mammogram or wellness visit at baseline were significantly more likely to report...

New Horizons in Advocacy Engaged Physical Sciences and Oncology Research

Thu, 18 May 2023 00:00:00 +0000

To address cancer as a multifaceted adaptive system, the increasing momentum for cross-disciplinary connectivity between cancer biologists, physical scientists, mathematicians, chemists, biomedical engineers, computer scientists, clinicians, and advocates is fueling the emergence of new scientific frontiers, principles, and opportunities within physical sciences and oncology. In parallel to highlighting the advances, challenges, and acceptance of advocates as credible contributors, we offer recommendations for addressing real world hurdles in advancing equitable partnerships among advocacy stakeholders.

Identification of tumor-autonomous and indirect effects of vitamin D action that inhibit breast cancer growth and tumor progression

Fri, 12 May 2023 00:00:00 +0000

Several epidemiological studies have found that low vitamin D levels are associated with worse prognosis and poorer outcomes in patients with breast cancer (BCa), although some studies have failed to find this association. In addition, prior research has found that BCa patients with vitamin D deficiency have a more aggressive molecular phenotype and worse prognostic biomarkers. As vitamin D deficiency is common in patients diagnosed with BCa, elucidating the cause of the association between poor outcomes and vitamin D deficiency promises to have a significant impact on improving care for patients with BCa including enabling the development of novel therapeutic approaches. Here we review our recent findings in this area, including our data revealing that reduction of the expression of the vitamin D receptor (Vdr) within BCa cells accelerates primary tumor growth and enables the development of metastases, demonstrating a tumor autonomous effect of vitamin D signaling to suppress...

Low-dose exposure to PBDE disrupts genomic integrity and innate immunity in mammary tissue

Mon, 3 Apr 2023 00:00:00 +0000

The low-dose mixture hypothesis of carcinogenesis proposes that exposure to an environmental chemical that is not individually oncogenic may nonetheless be capable of enabling carcinogenesis when it acts in concert with other factors. A class of ubiquitous environmental chemicals that are hypothesized to potentially function in this low-dose capacity are synthesized polybrominated diphenyl ethers (PBDEs). PBDEs can affect correlates of carcinogenesis that include genomic instability and inflammation. However, the effect of low-dose PBDE exposure on such correlates in mammary tissue has not been examined. In the present study, low-dose long-term (16 weeks) administration of PBDE to mice modulated transcriptomic indicators of genomic integrity and innate immunity in normal mammary tissue. PBDE increased transcriptome signatures for the Nuclear Factor Erythroid 2 Like 2 (NFE2L2) response to oxidative stress and decreased signatures for non-homologous end joining DNA repair (NHEJ)....

Rapid response nursing triage outcomes for COVID-19: factors associated with patient’s participation in triage recommendations

Thu, 30 Mar 2023 00:00:00 +0000

BackgroundCOVID-19 is an ongoing global health crisis with prevention and treatment recommendations rapidly changing. Rapid response telephone triage and advice services are critical in providing timely care during pandemics. Understanding patient participation with triage recommendations and factors associated with patient participation can assist in developing sensitive and timely interventions for receiving the treatment to prevent adverse health effects of COVID-19.MethodsThis cohort study aimed to assess patient participation (percentage of patients who followed nursing triage suggestions from the COVID hotline) and identify factors associated with patient participation in four quarterly electronic health records from March 2020 to March 2021 (Phase 1: 14 March 2020–6 June 2020; Phase 2: 17 June 2020–16 September 2020; Phase 3: 17 September 2020–16 December 2020; Phase 4: 17 December 2020–16 March 2021). All callers who provided their symptoms (including asymptomatic with...

Code OB: We need urgent action on climate change and toxic chemicals

Wed, 1 Feb 2023 00:00:00 +0000

Code OB: We need urgent action on climate change and toxic chemicals

The effect of COVID‐19 on telehealth: Next steps in a post‐pandemic life

Sun, 4 Dec 2022 00:00:00 +0000

Synopsis Older patients and those who require interpreters are least likely to use telehealth for gynecologic oncology care, showing disparities which continued after statewide vaccinations.

The Global Challenge to Prevent Breast Cancer: Surfacing New Ideas to Accelerate Prevention Research

Tue, 1 Nov 2022 00:00:00 +0000

Despite increases in screening and advances in treatment, breast cancer continues to be the most common cancer and cause of cancer deaths among women worldwide, and breast cancer rates have remained steady for decades. A new focus on population-level primary prevention is needed to tackle this disease at the most fundamental level. Unfortunately, only a small fraction of breast cancer research funds currently go to prevention. The California Breast Cancer Research Program (CBCRP) seeks to change this. In order to accelerate breast cancer primary prevention efforts, in 2018, CBCRP launched the Global Challenge to Prevent Breast Cancer, a prize competition to foster and disseminate new and innovative prevention research ideas. This Special Issue highlights the results of the Global Challenge and other CBCRP primary prevention efforts.

Immunogenicity and antitumor efficacy of a novel human PD-1 B-cell vaccine (PD1-Vaxx) and combination immunotherapy with dual trastuzumab/pertuzumab-like HER-2 B-cell epitope vaccines (B-Vaxx) in a syngeneic mouse model

Mon, 24 Oct 2022 00:00:00 +0000

Therapeutic blockade of PD-1/PD-L1 signaling with monoclonal antibodies (mAbs) has shown clinical success and activity across a broad set of cancer subtypes. However, monotherapy with PD-1/PD-L1 inhibitors are only effective in a subset of patients and ongoing studies show efficacy of treatment depends on a combinatorial approach. Contrary to mAbs chimeric B-cell cancer vaccines incorporating a "promiscuous" T-cell epitope have the advantage of producing a polyclonal B-cell antibody that can potentially induce memory B- and T-cell responses, while reducing immune evasion and suppression. Here, we describe a novel PD-1 B-cell peptide epitope vaccine (amino acid 92-110; PD1-Vaxx) linked to a measles virus fusion peptide (MVF) amino acid 288-302 via a four amino acid residue (GPSL) emulsified in Montanide ISA 720VG that aims to induce the production of polyclonal antibodies that block PD-1 signaling and thus trigger anticancer effects similar to nivolumab. In preclinical studies,...

FBXO44 promotes DNA replication-coupled repetitive element silencing in cancer cells

Mon, 24 Oct 2022 00:00:00 +0000

Repetitive elements (REs) compose ∼50% of the human genome and are normally transcriptionally silenced, although the mechanism has remained elusive. Through an RNAi screen, we identified FBXO44 as an essential repressor of REs in cancer cells. FBXO44 bound H3K9me3-modified nucleosomes at the replication fork and recruited SUV39H1, CRL4, and Mi-2/NuRD to transcriptionally silence REs post-DNA replication. FBXO44/SUV39H1 inhibition reactivated REs, leading to DNA replication stress and stimulation of MAVS/STING antiviral pathways and interferon (IFN) signaling in cancer cells to promote decreased tumorigenicity, increased immunogenicity, and enhanced immunotherapy response. FBXO44 expression inversely correlated with replication stress, antiviral pathways, IFN signaling, and cytotoxic T cell infiltration in human cancers, while a FBXO44-immune gene signature correlated with improved immunotherapy response in cancer patients. FBXO44/SUV39H1 were dispensable in normal cells....

Organophosphate and organohalogen flame retardant exposure and thyroid hormone disruption in women firefighters and office workers from San Francisco

Sat, 15 Oct 2022 00:00:00 +0000

Organophosphate and organohalogen flame retardant exposure and thyroid hormone disruption in women firefighters and office workers from San Francisco

Associations between social, biologic, and behavioral factors and biomarkers of oxidative stress during pregnancy: Findings from four ECHO cohorts

Sat, 15 Oct 2022 00:00:00 +0000

BACKGROUND: Lower socioeconomic status (SES) and elevated psychosocial stress are known contributors to adverse pregnancy outcomes; however, biological mechanisms linking these factors to adverse pregnancy outcomes are not well-characterized. Oxidative stress may be an important, yet understudied mechanistic pathway. We used a pooled study design to examine biological, behavioral, and social factors as predictors of prenatal oxidative stress biomarkers. METHODS: Leveraging four pregnancy cohorts from the Environmental influences on Child Health Outcomes (ECHO) Program spanning multiple geographic regions across the United States (U.S.) (N = 2082), we measured biomarkers of oxidative stress in urine samples at up to three time points during pregnancy, including 8-isoprostane-prostaglandin F_2α (8-isoPGF_2α), its major metabolite, 2,3-dinor-5,6-dihydro-15-F_2t-isoprostane, and prostaglandin F_2α (PGF_2α). Maternal age, pre-pregnancy...

Exposure to Contemporary and Emerging Chemicals in Commerce among Pregnant Women in the United States: The Environmental influences on Child Health Outcome (ECHO) Program

Sat, 23 Jul 2022 00:00:00 +0000

Prenatal chemical exposures can influence maternal and child health; however, few industrial chemicals are routinely biomonitored. We assessed an extensive panel of contemporary and emerging chemicals in 171 pregnant women across the United States (U.S.) and Puerto Rico in the Environmental influences on Child Health Outcomes (ECHO) Program. We simultaneously measured urinary concentrations of 89 analytes (103 total chemicals representing 73 parent compounds) in nine chemical groups: bactericides, benzophenones, bisphenols, fungicides and herbicides, insecticides, organophosphate esters (OPEs), parabens, phthalates/alternative plasticizers, and polycyclic aromatic hydrocarbons (PAHs). We estimated associations of creatinine-adjusted concentrations with sociodemographic and specimen characteristics. Among our diverse prenatal population (60% non-Hispanic Black or Hispanic), we detected 73 of 89 analytes in ≥1 participant and 36 in >50% of participants. Five analytes not currently...

Bisphenol A replacement chemicals, BPF and BPS, induce protumorigenic changes in human mammary gland organoid morphology and proteome

Fri, 22 Jul 2022 00:00:00 +0000

SignificanceBisphenol A (BPA), found in many plastic products, has weak estrogenic effects that can be harmful to human health. Thus, structurally related replacements-bisphenol S (BPS) and bisphenol F (BPF)-are coming into wider use with very few data about their biological activities. Here, we compared the effects of BPA, BPS, and BPF on human mammary organoids established from normal breast tissue. BPS disrupted organoid architecture and induced supernumerary branching. At a proteomic level, the bisphenols altered the abundance of common targets and those that were unique to each compound. The latter included proteins linked to tumor-promoting processes. These data highlighted the importance of testing the human health effects of replacements that are structurally related to chemicals of concern.

Organophosphate and Organohalogen Flame-Retardant Exposure and Thyroid Hormone Disruption in a Cross-Sectional Study of Female Firefighters and Office Workers from San Francisco

Fri, 22 Jul 2022 00:00:00 +0000

Occupational exposures to flame retardants (FRs), a class of suspected endocrine-disrupting compounds, are of health concern for firefighters. We sought to characterize exposure to FR compounds and evaluate their association with thyroid hormone levels, a biomarker of early effect, in female firefighters and office workers in San Francisco. In a cross-sectional study, we measured replacement organophosphate and organohalogen FRs in spot urine samples from firefighters (N = 86) and office workers (N = 84), as well as total thyroxine (T₄) and thyroid-stimulating hormone in plasma for 84 firefighters and 81 office workers. Median bis(1,3-dichloro-2-propyl)phosphate (BDCPP) levels were 5 times higher in firefighters than office workers. Among firefighters, a doubling of BDCPP was associated with a 2.88% decrease (95% confidence interval -5.28, -0.42) in T₄. We did not observe significant associations between FRs and T₄ among office workers....

Association of mammographic density with blood DNA methylation

Fri, 3 Jun 2022 00:00:00 +0000

BACKGROUND: Altered DNA methylation may be an intermediate phenotype between breast cancer risk factors and disease. Mammographic density is a strong risk factor for breast cancer. However, no studies to date have identified an epigenetic signature of mammographic density. We performed an epigenome-wide association study of mammographic density. METHODS: White blood cell DNA methylation was measured for 385 postmenopausal women using the Illumina Infinium MethylationEPIC BeadChip array. Differential methylation was assessed using genome-wide, probe-level, and regional analyses. We implemented a resampling-based approach to improve the stability of our findings. RESULTS: On average, women with elevated mammographic density exhibited DNA hypermethylation within CpG islands and gene promoters compared to women with lower mammographic density. We identified 250 CpG sites for which DNA methylation was significantly associated with mammographic density. The top sites were located within...

Evaluating the Impact of Language Concordance on Coronavirus Disease 2019 Contact Tracing Outcomes Among Spanish-Speaking Adults in San Francisco Between June and November 2020

Tue, 29 Mar 2022 00:00:00 +0000

We evaluated the impact of language concordance-clinician or public health worker fluency in a patient's primary language-on coronavirus disease 2019 (COVID-19) contact tracing outcomes among 2668 Spanish-speaking adults in San Francisco. Language concordance was associated with 20% greater odds of COVID-19 testing and 53% greater odds of support service referrals.

Effect of a Community-Based Medical Oncology Depression Screening Program on Behavioral Health Referrals Among Patients With Breast Cancer

Fri, 11 Feb 2022 00:00:00 +0000

Importance: Implementation of guideline-recommended depression screening in medical oncology remains challenging. Evidence suggests that multicomponent care pathways with algorithm-based referral and management are effective, yet implementation of sustainable programs remains limited and implementation-science guided approaches are understudied. Objective: To evaluate the effectiveness of an implementation-strategy guided depression screening program for patients with breast cancer in a community setting. Design, Setting, and Participants: A pragmatic cluster randomized clinical trial conducted within Kaiser Permanente Southern California (KPSC). The trial included 6 medical centers and 1436 patients diagnosed with new primary breast cancer who had a consultation with medical oncology between October 1, 2017, through September 30, 2018. Patients were followed up through study end date of May 31, 2019. Interventions: Six medical centers in Southern California participated and were...

Application of an in Vitro Assay to Identify Chemicals That Increase Estradiol and Progesterone Synthesis and Are Potential Breast Cancer Risk Factors

Fri, 15 Oct 2021 00:00:00 +0000

BACKGROUND: Established breast cancer risk factors, such as hormone replacement therapy and reproductive history, are thought to act by increasing estrogen and progesterone (P4) activity. OBJECTIVE: We aimed to use in vitro screening data to identify chemicals that increase the synthesis of estradiol (E2) or P4 and evaluate potential risks. METHOD: Using data from a high-throughput (HT) in vitro steroidogenesis assay developed for the U.S. Environmental Protection Agency (EPA) ToxCast program, we identified chemicals that increased estradiol (E2-up) or progesterone (P4-up) in human H295R adrenocortical carcinoma cells. We prioritized chemicals by their activity. We compiled in vivo studies and assessments about carcinogenicity and reproductive/developmental (repro/dev) toxicity. We identified exposure sources and predicted intakes from the U.S. EPA's ExpoCast. RESULTS: We found 296 chemicals increased E2 (182) or P4 (185), with 71 chemicals increasing...

Associations between polyfluoroalkyl substance and organophosphate flame retardant exposures and telomere length in a cohort of women firefighters and office workers in San Francisco

Mon, 6 Sep 2021 00:00:00 +0000

BackgroundEnvironmental chemical exposures can affect telomere length, which in turn has been associated with adverse health outcomes including cancer. Firefighters are occupationally exposed to many hazardous chemicals and have higher rates of certain cancers. As a potential biomarker of effect, we assessed associations between chemical exposures and telomere length in women firefighters and office workers from San Francisco, CA.MethodsWe measured serum concentrations of polyfluoroalkyl substances (PFAS), urinary metabolites of flame retardants, including organophosphate flame retardants (OPFRs), and telomere length in peripheral blood leukocytes in women firefighters (N = 84) and office workers (N = 79) who participated in the 2014–15 Women Workers Biomonitoring Collaborative. Multiple linear regression models were used to assess associations between chemical exposures and telomere length.ResultsRegression results revealed significant positive associations between...

Modality across genres in Spanish as a heritage language

Thu, 2 Sep 2021 00:00:00 +0000

Abstract Writers’ use of modality, an interpersonal linguistic resource commonly used for expressing probability, reveals key information about their claims. Most research on modality addresses L2 English learners, leaving a gap in research in advanced language development in other languages. This paper addresses this gap by studying how heritage language (HL) speakers of Spanish express doubt and probability in Spanish and how the lexicogrammatical features they use across genres reveal how they express these meanings. Drawing on Systemic Functional Linguistics and pragmatics, this study examines modality in 125 texts written in Spanish by HL students in the U.S., including narratives, expositions, article reviews, personal responses, and research papers. The results reveal that students use the most modality resources in personal responses and the least in reviews. This work offers insights about the interpersonal resources writers choose to express their argumentative...

Neighborhood Contexts and Breast Cancer Among Asian American Women

Thu, 8 Jul 2021 00:00:00 +0000

Background: This study examines how neighborhood socioeconomic status (nSES) and ethnic composition are associated with breast cancer risk for Asian American women. Methods: We linked individual level data from a population-based case–control study of breast cancer among Asian American women with neighborhood level data in the Greater San Francisco Bay Area (cases: n = 118, controls: n = 390). Multivariable logistic regression models examined the association between nSES, ethnic composition, and odds of having breast cancer. Results: Asian American women living in neighborhoods with high nSES and high ethnic composition had the highest odds of breast cancer, compared to those living in neighborhoods with high nSES and low ethnic composition (OR = 0.34, 95% CI [0.16–0.75]) or in neighborhoods with low nSES and high ethnic composition (OR = 0.37, 95% CI [0.17–0.83]). Discussion: Neighborhood socioeconomic and ethnic contexts are associated with breast cancer for Asian American women....

Biochemical Characterization of the Human Arsenite-stimulated ATPase (hASNA-I)*