Cancer progression is mediated by processes that are also important in wound repair. As a result, cancers have been conceptualized as overhealing wounds or "wounds do not heal," and gene expression signatures reflective of repair shown value predictors breast cancer survival. Despite the widespread acknowledgment commonalities between host responses to cancer, normal tissue adjacent well characterized.Using RNA extracted from histologically 107 patients, including 60 reduction mammoplasty...

We demonstrate the conjugation of cancer drug doxorubicin (DOX) to poly(methacryloyloxyethyl phosphorylcholine) (polyMPC), linked by hydrazone groups, using (1) a one-pot ATRP/click sequence, and (2) post-polymerization strategy. While method gave polyMPC–DOX conjugates in facile single step, higher-molecular-weight polymers with very high DOX loadings. release from polyMPC backbone was pH-dependent (faster at pH 5.0 than 7.4) owing linkage. Half-life values ranged 2 40 h 5.0. Cell culture...

Abstract IL-10 is a key pleiotropic cytokine that can both promote and curb Th2-dependent allergic responses. In this study, we demonstrate novel role for in promoting mast cell expansion the development of IgE-mediated food allergy. Oral OVA challenge sensitized BALB/c mice resulted robust intestinal response accompanied by diarrhea, activation, predominance Th2 cytokines, including enhanced expression. contrast, anaphylaxis, production, was significantly attenuated IL-10−/− compared with...

To evaluate immune responses to coronavirus disease 2019 (COVID-19) mRNA-based vaccines present in breast milk and transfer of the breastfeeding infants.We enrolled 30 lactating women who received COVID-19 from January through April 2021 this cohort study. Women provided serial samples, including expressed before vaccination, across 2-3 weeks after first dose, 3 second dose. their blood, spotted on cards (dried blood spots), 19 days dose 21 Stool samples breastfed infants were collected...

Background: Endocrine-disrupting chemicals have been shown to broad effects on development, but their mutagenic actions that can lead cancer less clearly demonstrated. Physiological levels of estrogen stimulate DNA damage in breast epithelial cells through mechanisms mediated by estrogen-receptor alpha (ERα). Benzophenone-3 (BP-3) and propylparaben (PP) are xenoestrogens found the urine >96% U.S. population. Objectives: We investigated effect BP-3 PP receptor–dependent transactivation at...

Recently, mitochondria have been suggested to act in tumor suppression. However, the underlying mechanisms by which suppress tumorigenesis are far from being clear. In this study, we investigated link between mitochondrial dysfunction and suppressor protein p53 using a set of respiration-deficient (Res−) mammalian cell mutants with impaired assembly oxidative phosphorylation machinery. Our data suggest that normal function is required for γ-irradiation (γIR)-induced death, mainly...

IgE antibodies and mast cells play critical roles in the establishment of allergic responses to food antigens. Curcumin, active ingredient curry spice turmeric, has anti-inflammatory properties, thus may have capacity regulate Th2 mucosal cell function during responses. We assessed whether curcumin ingestion oral allergen exposure can modulate development allergy using a murine model ovalbumin (OVA)-induced intestinal anaphylaxis. Herein, we demonstrate that frequent OVA inhibits...

The molecular mechanisms involved in the development of obesity and related complications remain unclear. Wnt signaling plays an important role preadipocyte differentiation adipogenesis. expression a antagonist, secreted frizzled protein 1 (SFRP1), is increased response to initial weight gain, then levels are reduced under conditions extreme both humans animals. Here we report that loss Sfrp1 exacerbates glucose homeostasis inflammation mice diet induced (DIO). Sfrp1(-/-) fed high fat (HFD)...

We report the in vivo efficacy, tumor-bearing mice, of cancer prodrugs consisting poly(methacryloyloxyethyl phosphorylcholine) (polyMPC) conjugated to doxorubicin (DOX). Our synthesis polyMPC–DOX conjugates established with tunable drug loading, pH sensitive release kinetics, and a maximum tolerated dose range 30–50 mg/kg (DOX equivalent) healthy mice. Here we show prolonged circulation polyMPC–DOX, measured half-life (t1/2) 8 times greater than that free drug. observed reduced uptake...

The Wnt family of secreted proteins is implicated in the regulation cell fate during development, as well proliferation, morphology, and migration. Aberrant activation Wnt/β-catenin signaling pathway leads to development several human cancers, including breast cancer. Secreted frizzled-related protein 1 (SFRP1) antagonizes this by competing with Frizzled receptor for ligands resulting an attenuation signal transduction cascade. Loss SFRP1 expression observed cancer, along other associated...

Abstract Breast cancer is a heterogeneous disease that varies in its biology and response to therapy. A foremost threat patients tumor invasion metastasis, with the greatest risk among diagnosed triple‐negative and/or basal‐like breast cancers. greater understanding of molecular mechanisms underlying cell spreading needed as 90% cancer‐associated deaths result from metastasis. We previously demonstrated Tamoxifen‐selected, MCF‐7 derivative, TMX2‐28, lacks expression estrogen receptor α (ERα)...

Transforming growth factor (TGF)-β plays a dual role during mammary gland development and tumorigenesis has been shown to stimulate epithelial-mesenchymal transition (EMT) as well cellular migration. The Wnt/β-catenin pathway is also implicated in EMT inappropriate activation of the signaling leads several human cancers, including breast cancer. Secreted frizzled-related protein 1 (SFRP1) antagonizes this loss SFRP1 expression frequently observed tumors cancer cell lines. We previously...

Abstract Background: Age is the strongest breast cancer risk factor, with overall increasing steadily beginning at approximately 30 years of age. However, while lower among younger women, young women's may be more aggressive. Although, several genomic and epidemiologic studies have shown higher prevalence aggressive, estrogen-receptor negative in age-related gene expression that predisposes to these tumors poorly understood. Characterizing patterns normal tissues provide insights on etiology...

Relationships of parity with breast cancer risk are complex. Parity is associated decreased postmenopausal hormone receptor–positive tumors, but may increase for basal-like cancers and early-onset tumors. Characterizing parity-related gene expression patterns in normal tumor tissues improve understanding the biological mechanisms underlying this complex pattern risk. We developed a signature by analyzing microRNA microarray data from 130 reduction mammoplasty (RM) patients (54 nulliparous 76...

Mast cells are highly versatile that perform a variety of functions depending on the immune trigger, context activation and cytokine stimulus. Antigen-mediated mast cell responses regulated by transcriptional processes result in induction numerous genes contributing to function. Recently, we also showed exposure dietary agents with known epigenetic actions such as curcumin can suppress cell-mediated food allergy, suggesting vivo may be epigenetically regulated. To further assess effects...

Background The IL-33/ST2 axis plays a pivotal role in the development of IgE-mediated mast cell (MC) responses during food allergy. We recently demonstrated that pleiotropic cytokine, IL-10, not only exerts proinflammatory effects on MC activation, but also promotes IL-33-induced responses. However, whether IL-33 is necessary for IL-10’s has been examined. Methods To therefore determine this pathway, we assessed IL-10 activation and allergy wild-type (WT) ST2 -/- mice. Results stimulation...

Abstract Background Secreted frizzled-related proteins (SFRPs) are a family of that block the Wnt signaling pathway and loss SFRP1 expression is found in breast cancer along with multitude other human cancers. Activated leads to inappropriate mammary gland development tumorigenesis mice. When knocked down immortalized non-malignant epithelial cells, cells exhibit malignant phenotype which resembles characteristics observed metastatic stem-like cells. However, effects on vivo yet be...

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

Atypical breast hyperplasias (AH) have a 10-year risk of progression to invasive cancer estimated at 4–7%, with the overall developing increased by ~ 4-fold. AH lesions are estrogen receptor alpha positive (ERα+) and represent indicators and/or precursor low grade ERα+ tumors. Therefore, molecular profiles offer insights into earliest changes in epithelium, rendering it susceptible oncogenic transformation. In this study, women were selected who diagnosed ductal or lobular AH, but no prior...

Background : Signaling by estrogen-receptor alpha (ERα) plays a major role in breast cancer initiation and ERα-mediated DNA damage has been implicated development of resistance to endocrine therapies. Investigations the mechanism mediated ERα signaling are carried out cell lines due lack ERα+ normal human epithelial cells (HBEC). Defining mechanisms which induces initiates tumorigenesis requires HBECs that express ERα, demonstrate estrogenic responses, amenable long term propagation culture....

Diverse compounds from many different chemical classes are currently targeted in preclinical analyses for their ability to act as both chemopreventative and chemotherapeutic agents. Phenolic phytochemicals Rhodiola crenulata has such potential. This species is a perennial plant that grows the Tundra, Siberia, high-elevation regions of Tibet. The phenolic secondary metabolites isolated R. were recently analyzed setting treat lymphosarcomas superficial bladder cancers. However, effects have...

Novel pentafluorophenyl (PFP)-ester-functionalized phosphorylcholine (PC) polymers of different architectures were prepared and conjugated to lysozyme as a model protein. Linear two-arm poly(2-methacryloyloxyethyl phosphorylcholine) (polyMPC) structures containing PFP functionality at the chain-end by atom transfer radical polymerization (ATRP) from novel initiators. Additional conjugates phosphorylcholine-substituted cyclooctene (PC-COE) PFP-ester bearing comonomers. The polymer–protein...