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https://www.readbyqxmd.com/read/28302531/resistin-potentiates-chemoresistance-and-stemness-of-breast-cancer-cells-implications-for-racially-disparate-therapeutic-outcomes
#1
Sachin K Deshmukh, Sanjeev K Srivastava, Haseeb Zubair, Arun Bhardwaj, Nikhil Tyagi, Ahmed Al-Ghadhban, Ajay P Singh, Donna L Dyess, James E Carter, Seema Singh
Breast cancer (BC) continues to be the most frequently diagnosed cancer in American women, which disproportionately affects women of African-American (AA) descent. Previously, we reported greater serum levels of resistin in AA BC patients relative to Caucasian-American (CA) patients, and established its role in growth and aggressiveness of breast tumor cells. Here we have investigated the role of resistin in BC-chemoresistance. MDA-MB-231 and MDA-MB-468 BC cells of CA and AA origin, respectively, were incubated with resistin prior to doxorubicin treatment...
March 13, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28300837/a-cd44v-subpopulation-of-breast-cancer-stem-like-cells-with-enhanced-lung-metastasis-capacity
#2
Jing Hu, Gang Li, Peiyuan Zhang, Xueqian Zhuang, Guohong Hu
Cancer stem-like cells (CSCs) are a subpopulation of cancer cells responsible for tumor growth, and recent evidence suggests that CSCs also contribute to cancer metastasis. However, the heterogeneity of CSCs in metastasis capacities is still unclear in breast cancer. Here we show that among the CD24(-)/CD44(+) breast CSCs, a subset expressing the variant isoform of CD44 (CD44v) displays significantly higher capacity of lung metastasis than that expressing the standard CD44 isoform CD44s. Increasing or reducing the CD44v/CD44s ratio of breast cancer cells by regulating the expression of epithelial splicing regulatory protein 1 (ESRP1) leads to promotion or suppression of lung metastasis without influencing cancer cell stemness...
March 16, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28299668/runx-genes-in-breast-cancer-and-the-mammary-lineage
#3
Nicholas Rooney, Alessandra I Riggio, Daniel Mendoza-Villanueva, Paul Shore, Ewan R Cameron, Karen Blyth
A full understanding of RUNX gene function in different epithelial lineages has been thwarted by the lethal phenotypes observed when constitutively knocking out these mammalian genes. However temporal expression of the Runx genes throughout the different phases of mammary gland development is indicative of a functional role in this tissue. A few studies have emerged describing how these genes impact on the fate of mammary epithelial cells by regulating lineage differentiation and stem/progenitor cell potential, with implications for the transformed state...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28299476/a-comparison-of-the-molecular-subtypes-of-triple-negative-breast-cancer-among-non-asian-and-taiwanese-women
#4
Ling-Ming Tseng, Jen-Hwey Chiu, Chun-Yu Liu, Yi-Fang Tsai, Yun-Lin Wang, Chu-Wen Yang, Yi-Ming Shyr
BACKGROUND: "Precision medicine" is a concept that by utilizing modern molecular diagnostics, an effective therapy is accurately applied for each cancer patient to improve their survival rates. The treatment of triple-negative breast cancer (TNBC) remains a challenging issue. The aim of this study was to compare the molecular subtypes of triple-negative breast cancer (TNBC) between Taiwanese and Non-Asian women. METHODS: GEO Datasets for non-Asian (12 groups, n = 1450) and Taiwanese (3 groups, n = 465) breast cancer, including 617 TNBC, were acquired, normalized and cluster analyzed...
March 15, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28298340/pre-clinical-validation-of-a-selective-anti-cancer-stem-cell-therapy-for-numb-deficient-human-breast-cancers
#5
Daniela Tosoni, Sarah Pambianco, Blanche Ekalle Soppo, Silvia Zecchini, Giovanni Bertalot, Giancarlo Pruneri, Giuseppe Viale, Pier Paolo Di Fiore, Salvatore Pece
The cell fate determinant Numb is frequently downregulated in human breast cancers (BCs), resulting in p53 inactivation and an aggressive disease course. In the mouse mammary gland, Numb/p53 downregulation leads to aberrant tissue morphogenesis, expansion of the stem cell compartment, and emergence of cancer stem cells (CSCs). Strikingly, CSC phenotypes in a Numb-knockout mouse model can be reverted by Numb/p53 restoration. Thus, targeting Numb/p53 dysfunction in Numb-deficient human BCs could represent a novel anti-CSC therapy...
March 15, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28297639/enhanced-directional-migration-of-cancer-stem-cells-in-3d-aligned-collagen-matrices
#6
Arja Ray, Zachary M Slama, Rachel K Morford, Samantha A Madden, Paolo P Provenzano
Directed cell migration by contact guidance in aligned collagenous extracellular matrix (ECM) is a critical enabler of breast cancer dissemination. The mechanisms of this process are poorly understood, particularly in 3D, in part because of the lack of efficient methods to generate aligned collagen matrices. To address this technological gap, we propose a simple method to align collagen gels using guided cellular compaction. Our method yields highly aligned, acellular collagen constructs with predictable microstructural features, thus providing a controlled microenvironment for in vitro experiments...
March 14, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28289331/screening-of-breast-cancer-stem-cell-inhibitors-using-a-protein-kinase-inhibitor-library
#7
Hack Sun Choi, Dal-Ah Kim, Heesung Chung, In Ho Park, Bo Hye Kim, Eok-Soo Oh, Duk-Hee Kang
BACKGROUND: Cancer stem cells (CSCs), a subpopulation in tumors, are known to cause drug resistance, tumor recurrence and metastasis. Based on the characteristic formation of mammospheres in in vitro conditions, the mammosphere formation assay has become an essential tool for quantifying CSC activity in breast cancer research. However, manual counting of mammospheres is a time-consuming process that is not amenable to high-throughput screening, and there are occasional inaccuracies in the process of determining the mammosphere diameter...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28281569/treating-triple-negative-breast-cancer-cells-with-erlotinib-plus-a-select-antioxidant-overcomes-drug-resistance-by-targeting-cancer-cell-heterogeneity
#8
Bin Bao, Cristina Mitrea, Priyanga Wijesinghe, Luca Marchetti, Emily Girsch, Rebecca L Farr, Julie L Boerner, Ramzi Mohammad, Greg Dyson, Stanley R Terlecky, Aliccia Bollig-Fischer
Among breast cancer patients, those diagnosed with the triple-negative breast cancer (TNBC) subtype have the worst prog-nosis. TNBC does not express estrogen receptor-alpha, progesterone receptor, or the HER2 oncogene; therefore, TNBC lacks targets for molecularly-guided therapies. The concept that EGFR oncogene inhibitor drugs could be used as targeted treatment against TNBC has been put forth based on estimates that 30-60% of TNBC express high levels of EGFR. However, results from clinical trials testing EGFR inhibitors, alone or in combination with cytotoxic chemotherapy, did not improve patient outcomes...
March 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28279922/biomaterial-enabled-delivery-of-sdf-1%C3%AE-at-the-ventral-side-of-breast-cancer-cells-reveals-a-crosstalk-between-cell-receptors-to-promote-the-invasive-phenotype
#9
Xi Qiu Liu, Laure Fourel, Fabien Dalonneau, Rabia Sadir, Salome Leal, Hugues Lortat-Jacob, Marianne Weidenhaupt, Corinne Albiges-Rizo, Catherine Picart
The SDF-1α chemokine (CXCL12) is a potent bioactive chemoattractant known to be involved in hematopoietic stem cell homing and cancer progression. The associated SDF-1α/CXCR4 receptor signaling is a hallmark of aggressive tumors, which can metastasize to distant sites such as lymph nodes, lung and bone. Here, we engineered a biomimetic tumoral niche made of a thin and soft polyelectrolyte film that can retain SDF-1α to present it, in a spatially-controlled manner, at the ventral side of the breast cancer cells...
February 27, 2017: Biomaterials
https://www.readbyqxmd.com/read/28273453/cd95-fas-increases-stemness-in-cancer-cells-by-inducing-a-stat1-dependent-type-i-interferon-response
#10
Abdul S Qadir, Paolo Ceppi, Sonia Brockway, Calvin Law, Liang Mu, Nikolai N Khodarev, Jung Kim, Jonathan C Zhao, William Putzbach, Andrea E Murmann, Zhuo Chen, Wenjing Chen, Xia Liu, Arthur R Salomon, Huiping Liu, Ralph R Weichselbaum, Jindan Yu, Marcus E Peter
Stimulation of CD95/Fas drives and maintains cancer stem cells (CSCs). We now report that this involves activation of signal transducer and activator of transcription 1 (STAT1) and induction of STAT1-regulated genes and that this process is inhibited by active caspases. STAT1 is enriched in CSCs in cancer cell lines, patient-derived human breast cancer, and CD95(high)-expressing glioblastoma neurospheres. CD95 stimulation of cancer cells induced secretion of type I interferons (IFNs) that bind to type I IFN receptors, resulting in activation of Janus-activated kinases, activation of STAT1, and induction of a number of STAT1-regulated genes that are part of a gene signature recently linked to therapy resistance in five primary human cancers...
March 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28270621/integrin-%C3%AE-4-identifies-cancer-stem-cell-enriched-populations-of-partially-mesenchymal-carcinoma-cells
#11
Brian Bierie, Sarah E Pierce, Cornelia Kroeger, Daniel G Stover, Diwakar R Pattabiraman, Prathapan Thiru, Joana Liu Donaher, Ferenc Reinhardt, Christine L Chaffer, Zuzana Keckesova, Robert A Weinberg
Neoplastic cells within individual carcinomas often exhibit considerable phenotypic heterogeneity in their epithelial versus mesenchymal-like cell states. Because carcinoma cells with mesenchymal features are often more resistant to therapy and may serve as a source of relapse, we sought to determine whether such cells could be further stratified into functionally distinct subtypes. Indeed, we find that a basal epithelial marker, integrin-β4 (ITGB4), can be used to enable stratification of mesenchymal-like triple-negative breast cancer (TNBC) cells that differ from one another in their relative tumorigenic abilities...
March 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28270600/diverse-regulation-of-mammary-epithelial-growth-and-branching-morphogenesis-through-noncanonical-wnt-signaling
#12
Kai Kessenbrock, Prestina Smith, Sander Christiaan Steenbeek, Nicholas Pervolarakis, Raj Kumar, Yasuhiro Minami, Andrei Goga, Lindsay Hinck, Zena Werb
The mammary gland consists of an adipose tissue that, in a process called branching morphogenesis, is invaded by a ductal epithelial network comprising basal and luminal epithelial cells. Stem and progenitor cells drive mammary growth, and their proliferation is regulated by multiple extracellular cues. One of the key regulatory pathways for these cells is the β-catenin-dependent, canonical wingless-type MMTV integration site family (WNT) signaling pathway; however, the role of noncanonical WNT signaling within the mammary stem/progenitor system remains elusive...
March 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28270510/down-regulation-of-forkhead-box-protein-a1-foxa1-leads-to-cancer-stem-cell-like-properties-in-tamoxifen-resistant-breast-cancer-cells-through-induction-of-interleukin-6
#13
Noritaka Yamaguchi, Yuji Nakayama, Naoto Yamaguchi
The selective estrogen receptor (ER) modulator tamoxifen inhibits ER signaling in breast cancer cells, and it is used for the treatment of ER-positive breast cancer. However, this type of cancer often acquires resistance to tamoxifen, and a better understanding of the molecular mechanisms underlying tamoxifen-resistance is required. In this study, we established tamoxifen-resistant (TAM-R) breast cancer cells by long-term tamoxifen treatment of ER-positive breast cancer MCF7 cells. In TAM-R cells, expression of not only ERα, a major form of ER in breast cancer, but also its transcriptional partner forkhead box protein A1 (FOXA1) was found to be reduced...
March 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28270406/akr1b1-promotes-basal-like-breast-cancer-progression-by-a-positive-feedback-loop-that-activates-the-emt-program
#14
Xuebiao Wu, Xiaoli Li, Qiang Fu, Qianhua Cao, Xingyu Chen, Mengjie Wang, Jie Yu, Jingpei Long, Jun Yao, Huixin Liu, Danping Wang, Ruocen Liao, Chenfang Dong
Basal-like breast cancer (BLBC) is associated with high-grade, distant metastasis and poor prognosis. Elucidating the determinants of aggressiveness in BLBC may facilitate the development of novel interventions for this challenging disease. In this study, we show that aldo-keto reductase 1 member B1 (AKR1B1) overexpression highly correlates with BLBC and predicts poor prognosis in breast cancer patients. Mechanistically, Twist2 transcriptionally induces AKR1B1 expression, leading to nuclear factor κB (NF-κB) activation...
March 7, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28270211/syndecan-1-is-a-novel-molecular-marker-for-triple-negative-inflammatory-breast-cancer-and-modulates-the-cancer-stem-cell-phenotype-via-the-il-6-stat3-notch-and-egfr-signaling-pathways
#15
Sherif Abdelaziz Ibrahim, Ramy Gadalla, Eslam A El-Ghonaimy, Omnia Samir, Hossam Taha Mohamed, Hebatallah Hassan, Burkhard Greve, Mohamed El-Shinawi, Mona Mostafa Mohamed, Martin Götte
BACKGROUND: Inflammatory breast cancer (IBC), a particularly aggressive form of breast cancer, is characterized by cancer stem cell (CSC) phenotype. Due to a lack of targeted therapies, the identification of molecular markers of IBC is of major importance. The heparan sulfate proteoglycan Syndecan-1 acts as a coreceptor for growth factors and chemokines, modulating inflammation, tumor progression, and cancer stemness, thus it may emerge as a molecular marker for IBC. METHODS: We characterized expression of Syndecan-1 and the CSC marker CD44, Notch-1 & -3 and EGFR in carcinoma tissues of triple negative IBC (n = 13) and non-IBC (n = 17) patients using qPCR and immunohistochemistry...
March 7, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28270035/bmi-1-promotes-self-renewal-of-radio-and-temozolomide-tmz-resistant-breast-cancer-cells
#16
Yanfang Yan, Ying Wang, Pengxin Zhao, Weiyuan Ma, Zhigang Hu, Kaili Zhang
Breast cancer is a hormone-dependent malignancy and is the most prevalent cause of cancer-related mortality among females. Radiation therapy and chemotherapy are common treatments of breast cancer. However, tumor relapse and metastasis following therapy are major clinical challenges. The importance of B-lymphoma Moloney murine leukemia virus insertion region-1 (BMI-1) was implicated in cell proliferation, stem cell maintenance, and tumor initiation. We established radio- and temozolomide (TMZ)-resistant (IRC-R) MCF-7 and MDA-MB-231 cell lines to investigate the mechanism involved in therapeutic resistance...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28265843/validity-of-self-reported-fertility-threatening-cancer-treatments-in-female-young-adult-cancer-survivors
#17
Samantha C Roberts, Amber Knight, Brian W Whitcomb, Jessica R Gorman, Andrew C Dietz, H Irene Su
PURPOSE: Detailed cancer treatment information is important to fertility and pregnancy care of female young adult cancer survivors. Accuracy of self-report of treatments that impact fertility and pregnancy is unknown. This study assessed agreement between self-report and medical records on receipt of fertility-threatening treatments. METHODS: A national cohort study of female young adult cancer survivors reported cancer treatments via Web-based questionnaires. Primary cancer treatment records were abstracted...
March 6, 2017: Journal of Cancer Survivorship: Research and Practice
https://www.readbyqxmd.com/read/28264701/zoledronic-acid-alters-hematopoiesis-and-generates-breast-tumor-suppressive-bone-marrow-cells
#18
Jessalyn M Ubellacker, Marie-Therese Haider, Molly J DeCristo, Gloria Allocca, Nicola J Brown, Daniel P Silver, Ingunn Holen, Sandra S McAllister
BACKGROUND: The bone-targeting agent zoledronic acid (ZOL) increases breast cancer survival in subsets of patients, but the underlying reasons for this protective effect are unknown. ZOL modulates the activity of osteoclasts and osteoblasts, which form hematopoietic stem cell niches, and therefore may affect hematopoietic cells that play a role in breast cancer progression. METHOD: Immunocompetent and immunocompromised strains of mice commonly used for breast cancer research were injected with a single, clinically relevant dose of ZOL (100 μg/kg) or vehicle control...
March 6, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28262977/metastatic-breast-cancer-cells-enter-into-dormant-state-and-express-cancer-stem-cells-phenotype-under-chronic-hypoxia
#19
Alessandra Carcereri de Prati, Elena Butturini, Antonella Rigo, Elisa Oppici, Michele Rossin, Diana Boriero, Sofia Mariotto
Tumor dormancy is a poorly understood stage in cancer progression characterized by mitotic cycle arrest in G0/G1 phase and low metabolism. The cells survive in a quiescent state and wait for appropriate environmental conditions to begin proliferation again giving rise to metastasis. Despite their key role in cancer development and metastasis, the knowledge about their biology and origin is still very limited due to the poorness of established in vitro models that faithfully recapitulated tumor dormancy. Using at least three cycles of 1%O2 hypoxia and reoxygenation, we establish and characterize the hypoxia-resistant human breast cancer cell line chMDA-MB-231 that can stably survive under 1% O2 condition by entering into dormant state characterized by arrest in G0/G1 phase and low metabolism...
March 6, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28260860/antiproliferation-effect-of-imatinib-mesylate-on-mcf7-t-47d-tumorigenic-and-mcf-10a-nontumorigenic-breast-cell-lines-via-pdgfr-%C3%AE-pdgf-bb-c-kit-and-scf-genes
#20
Ali Kadivar, Behnam Kamalidehghan, Hamid Akbari Javar, Benyamin Karimi, Reihaneh Sedghi, Mohamed Ibrahim Noordin
Recent cancer molecular therapies are targeting main functional molecules to control applicable process of cancer cells. Attractive targets are established by receptor tyrosine kinases, such as platelet-derived growth factor receptors (PDGFRs) and c-Kit as mostly irregular signaling, which is due to either over expression or mutation that is associated with tumorigenesis and cell proliferation. Imatinib mesylate is a selective inhibitor of receptor tyrosine kinase, including PDGFR-β and c-Kit. In this research, we studied how imatinib mesylate would exert effect on MCF7 and T-47D breast cancer and MCF 10A epithelial cell lines, the gene and protein expression of PDGFR-β, c-Kit and their relevant ligands platelet-derived growth factor (PDGF)-BB and stem cell factor (SCF)...
2017: Drug Design, Development and Therapy
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