PubMed Central (PMC3 - NLM DTD)
(2,081,148 recursos)
Archive of life sciences journal literature at the U.S. National Institutes of Health (NIH), developed and managed by NIH's National Center for Biotechnology Information (NCBI) in the National Library of Medicine (NLM).
Mostrando recursos 41 - 60 de 1,849
41.
HER2 therapy. HER2 (ERBB2): functional diversity from structurally conserved building blocks - Landgraf, Ralf
EGFR-type receptor tyrosine kinases achieve a broad spectrum of cellular responses by utilizing a set of structurally conserved building blocks. Based on available crystal structures and biochemical information, significant new insights have emerged into modes of receptor control, its deregulation in cancer, and the nuances that differentiate the four human receptors. This review gives an overview of current models of the control of receptor activity with a special emphasis on HER2 and HER3.
42.
Involvement of ?6?4 integrin in the mechanisms that regulate breast cancer progression - Bon, Giulia; Folgiero, Valentina; Di Carlo, Selene; Sacchi, Ada; Falcioni, Rita
Integrin ?6?4 is mostly expressed in epithelial tissues and endothelial and Schwann cells. Expression of ?6?4 is increased in many epithelial tumours, implicating its involvement in tumour malignancy. Moreover, this integrin activates several key signalling molecules in carcinoma cells, but its ability to activate the phosphatidylinositol 3-kinase/Akt pathway is among the mechanisms by which ?6?4 integrin regulates tumour behaviour. In this review we discuss the biological and clinical features of ?6?4 integrin that allow it to promote tumour survival and progression of mammary tumours.
43.
Key stages in mammary gland development. Secretory activation in the mammary gland: it's not just about milk protein synthesis! - Anderson, Steven M; Rudolph, Michael C; McManaman, James L; Neville, Margaret C
The transition from pregnancy to lactation is a critical event in the survival of the newborn since all the nutrient requirements of the infant are provided by milk. While milk contains numerous components, including proteins, that aid in maintaining the health of the infant, lactose and milk fat represent the critical energy providing elements of milk. Much of the research to date on mammary epithelial differentiation has focused upon expression of milk protein genes, providing a somewhat distorted view of alveolar differentiation and secretory activation. While expression of milk protein genes increases during pregnancy and at secretory activation, the genes...
44.
The continuing search for cancer-causing somatic mutations - Dalgliesh, Gillian L; Futreal, P Andrew
It is known that cancer is caused by an accumulation of mutations in DNA. Many genes have been associated with tumour progression either through germline or somatic mutations, but mutations in these genes by no means account for all instances of the disease. The availability of the completed human genome sequence and reduced costs of sequencing have allowed large-scale screens to uncover genes that are somatically mutated in cancer. In this issue, Chanock and colleagues present a screen of 91 breast cancers for somatic variants in a set of 21 genes.
45.
Lipid peroxidation, oxidative stress genes and dietary factors in breast cancer protection: a hypothesis - Gago-Dominguez, Manuela; Jiang, Xuejuan; Castelao, J Esteban
We have recently proposed that lipid peroxidation may be a common mechanistic pathway by which obesity and hypertension lead to increased renal cell cancer risk. During this exercise, we noted a risk factor swap between breast and kidney cancer (oophorectomy and increased parity, detrimental for kidney, beneficial for breast; high blood pressure, detrimental for kidney, beneficial for breast when it occurs during pregnancy; alcohol, beneficial for kidney, detrimental for breast, and so on). We have subsequently proposed the hypothesis that lipid peroxidation represents a protective mechanism in breast cancer, and reviewed the evidence of the role of lipid peroxidation on...
46.
An international initiative to identify genetic modifiers of cancer risk in BRCA1 and BRCA2 mutation carriers: the Consortium of Investigators of Modifiers of BRCA1 and BRCA2 (CIMBA) - Chenevix-Trench, Georgia; Milne, Roger L; Antoniou, Antonis C; Couch, Fergus J; Easton, Douglas F; Goldgar, David E;
BRCA1 and BRCA2 mutations exhibit variable penetrance that is likely to be accounted for, in part, by other genetic factors among carriers. However, studies aimed at identifying these factors have been limited in size and statistical power, and have yet to identify any convincingly validated modifiers of the BRCA1 and BRCA2 phenotype. To generate sufficient statistical power to identify modifier genes, the Consortium of Investigators of Modifiers of BRCA1 and BRCA2 (CIMBA) has been established. CIMBA contains about 30 affiliated groups who together have collected DNA and clinical data from approximately 10,000 BRCA1 and 5,000 BRCA2 mutation carriers. Initial efforts...
47.
The ethics of CYP2D6 testing for patients considering tamoxifen - Hartman, Anne-Renee; Helft, Paul
The CYP2D6 gene is responsible for the majority of tamoxifen metabolism. Recent compelling, yet limited data have determined that postmenopausal women who carry a functional polymorphism in the CYP2D6 gene have a worse clinical outcome than women who have a wild-type genotype. In this commentary we discuss the level of evidence needed to change clinical practice and whether CYP2D6 genotyping is appropriate for all women considering tamoxifen as part of their adjuvant therapy.
48.
Expression genomics in breast cancer research: microarrays at the crossroads of biology and medicine - Miller, Lance D; Liu, Edison T
Genome-wide expression microarray studies have revealed that the biological and clinical heterogeneity of breast cancer can be partly explained by information embedded within a complex but ordered transcriptional architecture. Comprising this architecture are gene expression networks, or signatures, reflecting biochemical and behavioral properties of tumors that might be harnessed to improve disease subtyping, patient prognosis and prediction of therapeutic response. Emerging 'hypothesis-driven' strategies that incorporate knowledge of pathways and other biological phenomena in the signature discovery process are linking prognosis and therapy prediction with transcriptional readouts of tumorigenic mechanisms that better inform therapeutic options.
49.
Gata-3 and mammary cell fate - Naylor, Matthew J; Ormandy, Christopher J
Genomic regulatory networks specify how cellular gene expression responds to external temporal and spatial stimuli, ensuring that correct cell fate decisions are made and the appropriate cell phenotypes are adopted. In mammary epithelial cells, the hierarchy of stem and progenitor cells and the genetically specified program of transcriptional activity are beginning to be elucidated and integrated. A novel role for Gata-3 in specifying and maintaining mammary cell fate has recently been identified. These reports offer an understanding of how mammary cells assume and maintain a variety of cell behaviours and functions, and how a mammary cell may potentially subvert these...
50.
Roles for estrogen and progesterone in breast cancer prevention - Jerry, D Joseph
Prevention has long been the holy grail of breast cancer research. The significant reduction in breast cancer risk afforded by a full-term pregnancy early in life suggests the great potential of preventive strategies. In contrast to the risks associated with prolonged exposures, exogenous estrogen and progesterone for short durations can mimic the protective effects of pregnancy in carcinogen-induced mammary tumor models. Rajkumar and coworkers have now demonstrated that these hormones protect mice from mammary tumors initiated by a spectrum of oncogenic alterations that are common in breast cancers. Although differences between rodent models and humans remain, the results reveal that...
51.
HER2 therapy. Small molecule HER-2 tyrosine kinase inhibitors - Spector, Neil; Xia, Wenle; El-Hariry, Iman; Yarden, Yossi; Bacus, Sarah
Overexpression of the human epidermal growth factor receptor (HER)-2 oncogenic receptor tyrosine kinase, which occurs in 25% of breast cancers, portends poor clinical outcome and consequently represents an attractive target for therapeutic intervention. Small molecule tyrosine kinase inhibitors that compete with ATP binding at the cytoplasmic catalytic kinase domain of HER-2 block autophosphorylation and activation of HER-2, resulting in inhibition of downstream proliferation and survival signals. These agents have exhibited clinical activity in patients with HER-2 overexpressing breast cancers. Here we review the development of HER-2 tyrosine kinase inhibitors, their mechanisms of action, their biological and clinical activities, their safety...
52.
HER-2/neu diagnostics in breast cancer - Carney, Walter P; Leitzel, Kim; Ali, Suhail; Neumann, Rainer; Lipton, Allan
HER-2/neu status of the primary breast cancer (PBC) is determined by immunohistochemistry and fluorescent in situ hybridization. Because of a variety of technical factors, however, the PBC may not accurately reflect the metastatic tumor in terms of HER-2/neu status. Recently published guidelines recommend that tumors be defined as HER-2/neu positive if 30% or more of the cells are 3+. Circulating levels of the HER-2 extracellular domain can be measured in serum using a test cleared by the US Food and Drug Administration, and increased serum HER-2/neu levels to above 15 ng/ml can reflect tumor progression. Studies comparing tissue HER-2/neu status...
53.
Cooperation between Wnt and Notch signalling in human breast cancer - Collu, Giovanna M; Brennan, Keith
The Wnt and Notch signalling pathways play major roles in mammary gland development and tumourigenesis. During development, these pathways have opposing effects. However, in a recent paper Ayyanan and coworkers show that expression of Wnt1 is sufficient to transform primary human mammary epithelial cells, and that this is in part due to activation of the Notch pathway. This indicates that during tumourigenesis the two pathways cooperate. Here we ask why activation of Wnt signalling alone is sufficient to cause transformation; whether there is evidence for inhibitory crosstalk between the pathways during tumourigenesis; and whether cooperation between these pathways occurs in...
54.
Human breast cancer stem cell markers CD44 and CD24: enriching for cells with functional properties in mice or in man? - Fillmore, Christine; Kuperwasser, Charlotte
Identification of breast cancer stem cells as the cells within breast tumors that have the ability to give rise to cells that make up the bulk of the tumor mass has shifted the focus of cancer research. However, there is still much debate concerning the unique nature of the markers that distinguish cancer stem cells in the breast. As such, understanding whether CD44+/CD24- breast cancer cells are merely more successful in overcoming an engraftment incompatibility that exists when injecting human cells into the mouse adipose tissue or are indeed bona fide cancer stem cells is of great importance.
55.
Tumour dormancy in breast cancer: an update - Brackstone, Muriel; Townson, Jason L; Chambers, Ann F
Delayed recurrences, common in breast cancer, are well explained by the concept of tumour dormancy. Numerous publications describe clinical times to disease recurrence or death, using mathematical approaches to infer mechanisms responsible for delayed recurrences. However, most of the clinical literature discussing tumour dormancy uses data from over a half century ago and much has since changed. This review explores how current breast cancer treatment could change our understanding of the biology of breast cancer tumour dormancy, and summarizes relevant experimental models to date. Current knowledge gaps are highlighted and potential areas of future research are identified.
56.
Inflammation and breast cancer. Microenvironmental factors regulating macrophage function in breast tumours: hypoxia and angiopoietin-2 - Lewis, Claire E; Hughes, Russell
Considerable evidence has now accumulated for tumour-associated macrophages stimulating key aspects of tumour progression, including the proliferation, survival and metastasis of tumour cells, tumour angiogenesis and suppression of the anti-tumour functions of other immune effectors at the tumour site. Tumour micro-environmental factors such as hypoxia have profound, direct effects on these cells, stimulating many of their pro-tumour functions. Hypoxia also does so indirectly by stimulating the release of the cytokine angiopoietin-2 from tumour cells and tumour blood vessels. This in turn then recruits Tie-2-expressing monocytes into tumours from the bloodstream and inhibits their production of anti-apoptotic and anti-angiogenic cytokines.
57.
Identification of women with an increased risk of developing radiation-induced breast cancer - Cardis, Elisabeth; Hall, Janet; Tavtigian, Sean V
In the previous issue of Breast Cancer Research, Broeks and collaborators present the results of a study suggesting that germline mutations in BRCA1, BRCA2, ATM or CHEK2 may double the risk of radiation-induced contralateral breast cancer following radiotherapy for a first breast cancer. The assocation appeared to be strongest among women who were below the age of 40 at the time of their first breast cancer and among women who developed their second cancer 5 years or more after the first. While there were a number of methodological issues that might limit the conclusions drawn from this paper, this is...
58.
Estrogen receptor-?: why may it influence clinical outcome in estrogen receptor-? positive breast cancer? - Shupnik, Margaret A
In the previous issue of the journal, Lin and coworkers present data demonstrate that increased expression of estrogen receptor (ER)-? in ER-?-positive breast cancer cells antagonizes a defined group of ER-?/estrogen stimulated genes that are involved in cell cycle regulation and DNA replication. Similar expression patterns for these genes were found human ER-? positive breast tumors expressing higher levels or ER-?, and this correlated with better clinical outcome. The implications for these data, which suggest that ER-? is a positive actor and diagnostic marker for therapeutic outcome, are discussed.
59.
Inflammation and breast cancer. Cyclooxygenase/prostaglandin signaling and breast cancer - Howe, Louise R
Many human cancers exhibit elevated prostaglandin (PG) levels due to upregulation of cyclooxygenase-2 (COX-2), a key enzyme in eicosanoid biosynthesis. COX-2 over-expression has been observed in about 40% of cases of invasive breast carcinoma and at a higher frequency in preinvasive ductal carcinoma in situ tumors, Extensive pharmacologic and genetic evidence implicates COX enzymes in neoplasia. Epidemiologic analyses demonstrate a protective effect of COX-inhibiting nonsteroidal anti-inflammatory drugs with respect to human cancer. Complementary experimental studies have established that both conventional nonsteroidal anti-inflammatory drugs and selective COX-2 inhibitors suppress mammary tumor formation in rodent breast cancer models. Furthermore, knocking out Cox-2...
60.
Decline in breast cancer incidence due to removal of promoter: combination estrogen plus progestin - Colditz, Graham A
Combination estrogen plus progestin causes breast cancer. In light of this causal relation, the rapid decline in breast cancer incidence noted in 2003, following an earlier and slower reduction in incidence from 1999, raises important issues regarding the proportion of this decline that may be due to a reduction in the use of combination therapy by postmenopausal women. The context of these national trends is reviewed and the strong link to the use of hormone therapy is discussed, after noting that screening cannot explain any substantial component of these trends. The rapid decrease in incidence, most evident among women aged...
41.
