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Estrogen Receptor Macrophages Breast Cancer

Nguyen Thi Thuy Ngan, Nguyen Thi Hoang Mai, Nguyen Le Nhu Tung, Nguyen Phu Huong Lan, Luong Thi Hue Tai, Nguyen Hoan Phu, Nguyen Van Vinh Chau, Tran Quang Binh, Le Quoc Hung, Justin Beardsley, Nicholas White, David Lalloo, Damian Krysan, William Hope, Ronald Geskus, Marcel Wolbers, Le Thanh Hoang Nhat, Guy Thwaites, Evelyne Kestelyn, Jeremy Day
Background : Cryptococcal meningitis is a leading cause of death in HIV-infected patients. International treatment guidelines recommend induction therapy with amphotericin B and flucytosine. This antifungal combination is most effective, but unfortunately flucytosine is expensive and unavailable where the burden of disease is greatest. Where unavailable, guidelines recommend treatment with amphotericin and fluconazole, but this is less effective, with mortality rates of 40-50%. Faster rates of clearance of yeast from cerebrospinal fluid (CSF) are associated with better outcomes - improving the potency of antifungal therapy is likely to be an effective strategy to improve survival...
2019: Wellcome Open Research
Sepideh Parvizpour, Jafar Razmara, Mohammad M Pourseif, Yadollah Omidi
Introduction: Triple-negative breast cancer (TNBC) is an important subtype of breast cancer, which occurs in the absence of estrogen, progesterone and HER-2 receptors. According to the recent studies, TNBC may be a cancer testis antigen (CTA)-positive tumor, indicating that the CTA-based cancer vaccine can be a treatment option for the patients bearing such tumors. Of these antigens (Ags), the MAGE-A family and NY-ESO-1 as the most immunogenic CTAs are the potentially relevant targets for the development of an immunotherapeutic way of the breast cancer treatment...
2019: BioImpacts: BI
Andrés M Castellaro, María C Rodriguez-Baili, Cecilia E Di Tada, Germán A Gil
Antiestrogenic adjuvant treatments are first-line therapies in patients with breast cancer positive for estrogen receptor (ER+). Improvement of their treatment strategies is needed because most patients eventually acquire endocrine resistance and many others are initially refractory to anti-estrogen treatments. The tumor microenvironment plays essential roles in cancer development and progress; however, the molecular mechanisms underlying such effects remain poorly understood. Breast cancer cell lines co-cultured with TNF-α-conditioned macrophages were used as pro-inflammatory tumor microenvironment models...
February 6, 2019: Cancers
Harikrishna Nakshatri, Brijesh Kumar, Heather N Burney, Mary L Cox, Max Jacobsen, George E Sandusky, Crislyn D'Souza-Schorey, Anna Maria V Storniolo
PURPOSE: Genetic ancestry influences evolutionary pathways of cancers. However, whether ancestry influences cancer-induced field defects is unknown. The goal of this study was to utilize ancestry-mapped true normal breast tissues as controls to identify cancer-induced field defects in normal tissue adjacent to breast tumors (NATs) in women of African American (AA) and European (EA) ancestry. EXPERIMENTAL DESIGN: A tissue microarray (TMA) comprising breast tissues of ancestry-mapped 100 age-matched healthy women from the Komen Tissue Bank (KTB) at Indiana University and tumor-NAT pairs from 100 women (300 samples total) was analyzed for the levels of ZEB1, an oncogenic transcription factor that is central to cell fate, mature luminal cell enriched estrogen receptor alpha (ERa), GATA3, FOXA1 and for immune cell composition...
February 4, 2019: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Ayse Basak Engin, Atilla Engin, Ipek Isik Gonul
Adipose tissue is the primary source of many pro-inflammatory cytokines in obesity. Macrophage numbers and pro-inflammatory gene expression are positively associated with adipocyte size. Free fatty acid- and tumor necrosis factor-α involving vicious cycle between adipocytes and macrophages aggravates inflammatory changes. Thereby, M1 macrophages form a characteristic "crown-like structures (CLSs)" around necrotic adipocytes in obese adipose tissue. In obese women, CLSs of breast adipose tissue are responsible for both increase in local aromatase activity, and aggressive behavior of breast cancer cells...
January 1, 2019: Journal of Molecular Endocrinology
Vasiliki Pelekanou, Franz Villarroel-Espindola, Kurt A Schalper, Lajos Pusztai, David L Rimm
BACKGROUND: The role of tumor-associated macrophages (TAMs) in the cancer immune landscape and their potential as treatment targets or modulators of response to treatment are gaining increasing interest. TAMs display high molecular and functional complexity. Therefore their objective assessment as breast cancer biomarkers is critical. The aims of this study were to objectively determine the in situ expression and significance of TAM biomarkers (CD68, CD163, and MMP-9) in breast cancer and to identify subclasses of patients who could benefit from TAM-targeting therapies...
December 17, 2018: Breast Cancer Research: BCR
Ernesto Cortes, Muge Sarper, Benjamin Robinson, Dariusz Lachowski, Antonios Chronopoulos, Stephen D Thorpe, David A Lee, Armando E Del Río Hernández
The mechanical properties of the tumor microenvironment are emerging as attractive targets for the development of therapies. Tamoxifen, an agonist of the G protein-coupled estrogen receptor (GPER), is widely used to treat estrogen-positive breast cancer. Here, we show that tamoxifen mechanically reprograms the tumor microenvironment through a newly identified GPER-mediated mechanism. Tamoxifen inhibits the myofibroblastic differentiation of pancreatic stellate cells (PSCs) in the tumor microenvironment of pancreatic cancer in an acto-myosin-dependent manner via RhoA-mediated contractility, YAP deactivation, and GPER signaling...
December 11, 2018: EMBO Reports
Marcelo Sobral-Leite, Koen Van de Vijver, Magali Michaut, Rianne van der Linden, Gerrit K J Hooijer, Hugo M Horlings, Tesa M Severson, Anna Marie Mulligan, Nayana Weerasooriya, Joyce Sanders, Annuska M Glas, Diederik Wehkamp, Lorenza Mittempergher, Kelly Kersten, Ashley Cimino-Mathews, Dennis Peters, Erik Hooijberg, Annegien Broeks, Marc J van de Vijver, Rene Bernards, Irene L Andrulis, Marleen Kok, Karin E de Visser, Marjanka K Schmidt
To better understand the expression pattern of programmed death-ligand 1 (PD-L1) expression in different breast cancer types, we characterized PD-L1 expression in tumor and tumor-infiltrating immune cells, in relation to mutation rate, BRCA1 -like status and survival. We analyzed 410 primary treatment-naive breast tumors comprising 162 estrogen receptor-positive (ER+) and HER2-, 101 HER2+ and 147 triple-negative (TN) cancers. Pathologists quantified tumor-infiltrating lymphocytes (TILs) and PD-L1 expression in tumor cells and TILs using whole slides and tissue microarray...
2018: Oncoimmunology
Lishan Zhang, Ming Liu, Jinglei Liu, Xingkai Li, Ming Yang, Benhua Su, Yanliang Lin
27-Hydroxycholesterol (27-HC) has been implicated in the pathological process of estrogen receptor positive breast cancer. However, the role of 27-HC in lung adenocarcinoma is still unclear. Because bone metastasis is a main reason for the high mortality of lung adenocarcinoma, this study aimed to investigate the effect of 27-HC on osteoclastogenesis in lung adenocarcinoma microenvironment. The results showed that the conditioned media (CM) from lung adenocarcinoma cells cocultured with macrophages promoted osteoclast differentiation, which was enhanced by 27-HC...
December 3, 2018: Journal of Cellular Physiology
Min Yao, Wei Fang, Curtis Smart, Qingting Hu, Shixia Huang, Nehemiah Alvarez, Patrick Fields, Nikki Cheng
Basal-like breast cancers are an aggressive breast cancer subtype, which often lack estrogen receptor, progesterone receptor and Her2 expression, and are resistant to anti-hormonal and targeted therapy, resulting in few treatment options. Understanding the underlying mechanisms that regulate progression of basal-like breast cancers would lead to new therapeutic targets and improved treatment strategies. Breast cancer progression is characterized by inflammatory responses, regulated in part by chemokines. The CCL2/CCR2 chemokine pathway is best known for regulating breast cancer progression through macrophage dependent mechanisms...
November 16, 2018: Molecular Cancer Research: MCR
Taryn L Cranford, Kandy T Velázquez, Reilly T Enos, Alexander T Sougiannis, Jackie E Bader, Meredith S Carson, Rebecca R Bellone, Ioulia Chatzistamou, Mitzi Nagarkatti, E Angela Murphy
Clinical studies provide strong evidence that obesity and associated adipose tissue (AT) inflammation are risk factors for breast cancer (BrCA); however, mechanistic knowledge of the interaction of obesity, BrCA, and menopausal status has proven to be not only lacking, but contradictory. Obesity-induced inflammation and elevated biosynthesis of estrogens, through aromatase-mediated metabolism of precursors, have been linked with hormone receptor positive (HP) postmenopausal BrCA but not previously associated with premenopausal BrCA risk...
November 2, 2018: Cancer Biology & Therapy
Laura W Bowers, Claire G Lineberger, Nikki A Ford, Emily L Rossi, Arunima Punjala, Kristina K Camp, Bruce K Kimler, Carol J Fabian, Stephen D Hursting
PURPOSE: Exposure to the polyphenolic plant lignan secoisolariciresinol diglucoside (SDG) and its metabolite enterolactone (ENL) has been associated with reduced breast cancer progression, particularly for estrogen receptor alpha (ERα)-negative disease, and decreased preclinical mammary tumor growth. However, while preclinical studies have established that SDG and ENL affect measures of progression in models of triple-negative breast cancer (TNBC, a subset of ERα-negative disease), the molecular mechanisms underlying these effects remain unclear...
October 26, 2018: Breast Cancer Research and Treatment
Wenyong Tan, Ming Yang, Hongli Yang, Fangbin Zhou, Weixi Shen
Neoadjuvant therapy (NAT) has been used increasingly in patients with locally advanced or early-stage breast cancer. However, the accurate evaluation and prediction of response to NAT remain the great challenge. Biomarkers could prove useful to identify responders or nonresponders, or even to distinguish between early and delayed responses. These biomarkers could include markers from the tumor itself, such as versatile proteins, genes, and ribonucleic acids, various biological factors or peripheral blood cells, and clinical and pathological features...
2018: Cancer Management and Research
Pengzhi Dong, Bing Yu, Lanlan Pan, Xiaoxuan Tian, Fangfang Liu
Purpose: Triple-negative breast cancer refers to breast cancer that does not express estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor 2 (Her2). This study aimed to identify the key pathways and genes and find the potential initiation and progression mechanism of triple-negative breast cancer (TNBC). Methods: We downloaded the gene expression profiles of GSE76275 from Gene Expression Omnibus (GEO) datasets. This microarray Super-Series sets are composed of gene expression data from 265 samples which included 67 non-TNBC and 198 TNBC...
2018: BioMed Research International
Wentao Ning, Zhiye Hu, Chu Tang, Lu Yang, Silong Zhang, Chune Dong, Jian Huang, Hai-Bing Zhou
In this work, we developed a small library of novel OBHS-RES hybrid compounds with dual inhibition activities targeting both the estrogen receptor α (ERα) and NF-κB by incorporating resveratrol (RES), a known inhibitor of NF-κB, into a privileged indirect antagonism structural motif (OBHS, oxabicycloheptene sulfonate) of estrogen receptor (ER). The OBHS-RES conjugates could bind well to ER and showed remarkable ERα antagonistic activity, and they also exhibited excellent NO inhibition in macrophage RAW 264...
September 27, 2018: Journal of Medicinal Chemistry
Wenzhe Song, Parth Thakor, David A Vesey, Glenda C Gobe, Christudas Morais
Disparate roles exist for tumor-associated macrophages in breast cancer growth and progression. The aim of this study was to explore the influence of induced macrophages on the growth of breast cancer cells. THP-1 monocytes were differentiated to macrophages using phorbol 12-myristate 13-acetate. The effect of the medium from THP-1 monocytes or macrophage-conditioned medium (MφCM) on MCF-7 (estrogen receptor and progesterone-positive positive) and MDA-MB-231 (MB; triple-negative) breast cancer cells was determined at 24 h, 48 h and 72 h...
October 2018: Biomedicine & Pharmacotherapy
Lirit N Franks, Benjamin M Ford, Toshifumi Fujiwara, Haibo Zhao, Paul L Prather
Selective estrogen receptor modulators (SERMs) target estrogen receptors (ERs) to treat breast cancer and osteoporosis. Several SERMs exhibit anti-cancer activity not related to ERs. To discover novel anti-cancer drugs acting via ER-independent mechanisms, derivatives of the SERM tamoxifen, known as the "ridaifen" compounds, have been developed that exhibit reduced or no ER affinity, while maintaining cytotoxicity. Tamoxifen and other SERMs bind to cannabinoid receptors with moderate affinity. Therefore, ER-independent effects of SERMs might be mediated via cannabinoid receptors...
June 12, 2018: Toxicology and Applied Pharmacology
Erin D Giles, Sonali Jindal, Elizabeth A Wellberg, Troy Schedin, Steven M Anderson, Ann D Thor, Dean P Edwards, Paul S MacLean, Pepper Schedin
BACKGROUND: Obesity and type II diabetes are linked to increased breast cancer risk in postmenopausal women. Patients treated with the antidiabetic drug metformin for diabetes or metabolic syndrome have reduced breast cancer risk, a greater pathologic complete response to neoadjuvant therapy, and improved breast cancer survival. We hypothesized that metformin may be especially effective when targeted to the menopausal transition, as this is a lifecycle window when weight gain and metabolic syndrome increase, and is also when the risk for obesity-related breast cancer increases...
June 14, 2018: Breast Cancer Research: BCR
Anbok Lee, Kyu Yeoun Won, Sung-Jig Lim, Sun Young Cho, Sang-Ah Han, SaeGwang Park, Jeong-Yoon Song
Many studies have reported that Aldehyde dehydrogenase 1 (ALDH1) and tumor-infiltrating lymphocytes (TIL) are related to breast cancer prognosis. However, the clinical significance of ALDH1 and tumor-infiltrating immune cells in breast cancer has not been fully investigated in patients who received neoadjuvant chemotherapy (NAC). We studied the significance of the expression of ALDH1 and the population of TIL for predicting the prognosis and chemotherapeutic response of patients with breast cancer who had received NAC...
May 2018: Pathology, Research and Practice
Yoon Jin Cha, Eun-Sol Kim, Ja Seung Koo
PURPOSE: We aimed to evaluate macrophage infiltration and to identify the status of crown-like structures (CLSs) in mammary adipose tissue of human breast tissue in cases with and without breast cancer. METHODS: Breast adipose tissue was obtained from reduction mammoplasty (N = 56, Group 1), non-neoplastic breast tissue of breast cancer patients (N = 84, Group 2), and breast cancer with adipose stroma (N = 140, Group 3). Immunohistochemical staining of CD68 and CD163 was performed, and the infiltrating macrophages and CLSs within breast adipose tissue were evaluated...
July 2018: Breast Cancer Research and Treatment
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