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https://www.readbyqxmd.com/read/28108628/metabolic-reprogramming-by-folate-restriction-leads-to-a-less-aggressive-cancer-phenotype
#1
Zahra Ashkavand, Ciara O'Flanagan, Mirko Hennig, Xiuxia Du, Stephen D Hursting, Sergey A Krupenko
: Folate coenzymes are involved in biochemical reactions of one-carbon transfer, and deficiency of this vitamin impairs cellular proliferation, migration, and survival in many cell types. Here, the effect of folate restriction on mammary cancer was evaluated using three distinct breast cancer subtypes differing in their aggressiveness and metastatic potential: noninvasive basal-like (E-Wnt), invasive but minimally metastatic claudin-low (M-Wnt), and highly metastatic claudin-low (metM-Wnt(liver)) cell lines, each derived from the same pool of MMTV-Wnt-1 transgenic mouse mammary tumors...
January 20, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28108626/a-new-role-for-er%C3%AE-silencing-via-dna-methylation-of-basal-stem-cell-and-emt-genes
#2
Eric A Ariazi, John C Taylor, Michael A Black, Emmanuelle Nicolas, Michael J Slifker, Diana J Azzam, Jeff Boyd
: Resistance to hormonal therapies is a major clinical problem in the treatment of estrogen receptor α-positive (ERα(+)) breast cancers. Epigenetic marks, namely DNA methylation of cytosine at specific CpG sites (5mCpG), are frequently associated with ERα(+) status in human breast cancers. Therefore, ERα may regulate gene expression in part via DNA methylation. This hypothesis was evaluated using a panel of breast cancer cell line models of antiestrogen resistance. Microarray gene expression profiling was used to identify genes normally silenced in ERα(+) cells but derepressed upon exposure to the demethylating agent decitabine, derepressed upon long-term loss of ERα expression, and resuppressed by gain of ERα activity/expression...
November 15, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28108518/a-transposon-based-analysis-reveals-rasa1-is-involved-in-triple-negative-breast-cancer
#3
Cristian Suárez-Cabrera, Rita M Quintana, Ana Bravo, M LLanos Casanova, Angustias Page, Josefa P Alameda, Jesus M Paramio, Alicia Maroto, Javier Salamanca, Adam J Dupuy, Angel Ramírez, Manuel Navarro
RAS genes are mutated in 20% of human tumors, but these mutations are very rare in breast cancer. Here we used a mouse model to generate tumors upon activation of a mutagenic T2Onc2 transposon via expression of a transposase driven by the keratin K5 promoter in a p53+/- background. These animals mainly developed mammary tumors, most of which had transposon insertions in one of two RASGAP genes, neurofibromin1 (NF1) and RAS p21 protein activator (Rasa1). Immunohistochemical analysis of a collection of human breast tumors confirmed that low expression of RASA1 is frequent in basal (triple-negative) and ER-negative tumors...
January 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28108512/constitutive-notch3-signaling-promotes-the-growth-of-basal-breast-cancers
#4
Lisa Choy, Thijs Hagenbeek, Margaret Solon, Dorothy M French, David Finkle, Amy Shelton, Rayna Venook, Matthew J Brauer, Christian W Siebel
Notch ligands signal through one of four receptors on neighboring cells to mediate cell-cell communication and control cell fate, proliferation and survival. Although aberrant Notch activation has been implicated in numerous malignancies, including breast cancer, the importance of individual receptors in distinct breast cancer subtypes and the mechanisms of receptor activation remain unclear. Using a novel antibody to detect active NOTCH3, we report here that NOTCH3 signals constitutively in a panel of basal breast cancer cell lines and in more than one-third of basal tumors...
January 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28108284/first-line-pazopanib-in-non-clear-cell-renal-carcinoma-the-italian-retrospective-multicenter-panorama-study
#5
Sebastiano Buti, Melissa Bersanelli, Francesca Maines, Gaetano Facchini, Francesco Gelsomino, Fable Zustovich, Matteo Santoni, Elena Verri, Ugo De Giorgi, Cristina Masini, Franco Morelli, Maria Giuseppa Vitale, Teodoro Sava, Giuseppe Prati, Carmelinda Librici, Anna Paola Fraccon, Giuseppe Fornarini, Marco Maruzzo, Francesco Leonardi, Orazio Caffo
INTRODUCTION: Pazopanib is a standard first-line treatment for metastatic clear-cell renal cell carcinoma (ccRCC). Very few data on its activity in non-clear-cell renal cell carcinoma (nccRCC) are currently available. The aim of this study was to retrospectively analyze efficacy and toxicity of pazopanib in nccRCC patients. PATIENTS AND METHODS: Records from advanced nccRCC patients (consecutive sample) treated with first-line pazopanib between 2010 and 2015 at 17 Italian centers were reviewed...
December 29, 2016: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28104682/out-ranking-brca1-in-mutation-carriers
#6
REVIEW
Emma Nolan, Geoffrey J Lindeman, Jane E Visvader
Beyond prophylactic mastectomy, there are currently very few options available to BRCA1 mutation carriers to help reduce their risk of developing breast cancer. An effective prevention therapy therefore remains a pressing area of need. Accumulating evidence points to amplification of the progesterone signaling axis in precancerous tissue from BRCA1 mutation carriers. Given that RANKL is an important paracrine mediator of hormonal signaling in breast tissue, there has been considerable interest in exploring a potential role for this pathway in oncogenesis...
January 19, 2017: Cancer Research
https://www.readbyqxmd.com/read/28102366/aurora-kinase-a-is-a-biomarker-for-bladder-cancer-detection-and-contributes-to-its-aggressive-behavior
#7
Aaron Mobley, Shizhen Zhang, Jolanta Bondaruk, Yan Wang, Tadeusz Majewski, Nancy P Caraway, Li Huang, Einav Shoshan, Guermarie Velazquez-Torres, Giovanni Nitti, Sangkyou Lee, June Goo Lee, Enrique Fuentes-Mattei, Daniel Willis, Li Zhang, Charles C Guo, Hui Yao, Keith Baggerly, Yair Lotan, Seth P Lerner, Colin Dinney, David McConkey, Menashe Bar-Eli, Bogdan Czerniak
The effects of AURKA overexpression associated with poor clinical outcomes have been attributed to increased cell cycle progression and the development of genomic instability with aneuploidy. We used RNA interference to examine the effects of AURKA overexpression in human bladder cancer cells. Knockdown had minimal effects on cell proliferation but blocked tumor cell invasion. Whole genome mRNA expression profiling identified nicotinamide N-methyltransferase (NNMT) as a downstream target that was repressed by AURKA...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28102225/glucocorticoid-receptor-signalling-activates-yap-in-breast-cancer
#8
Giovanni Sorrentino, Naomi Ruggeri, Alessandro Zannini, Eleonora Ingallina, Rebecca Bertolio, Carolina Marotta, Carmelo Neri, Elisa Cappuzzello, Mattia Forcato, Antonio Rosato, Miguel Mano, Silvio Bicciato, Giannino Del Sal
The Hippo pathway is an oncosuppressor signalling cascade that plays a major role in the control of cell growth, tissue homoeostasis and organ size. Dysregulation of the Hippo pathway leads to aberrant activation of the transcription co-activator YAP (Yes-associated protein) that contributes to tumorigenesis in several tissues. Here we identify glucocorticoids (GCs) as hormonal activators of YAP. Stimulation of glucocorticoid receptor (GR) leads to increase of YAP protein levels, nuclear accumulation and transcriptional activity in vitro and in vivo...
January 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28102194/%C3%AE-3-chains-of-type-v-collagen-regulate-breast-tumour-growth-via-glypican-1
#9
Guorui Huang, Gaoxiang Ge, Valerio Izzi, Daniel S Greenspan
Pericellular α3(V) collagen can affect the functioning of cells, such as adipocytes and pancreatic β cells. Here we show that α3(V) chains are an abundant product of normal mammary gland basal cells, and that α3(V) ablation in a mouse mammary tumour model inhibits mammary tumour progression by reducing the proliferative potential of tumour cells. These effects are shown to be primarily cell autonomous, from loss of α3(V) chains normally produced by tumour cells, in which they affect growth by enhancing the ability of cell surface proteoglycan glypican-1 to act as a co-receptor for FGF2...
January 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28099150/elimination-of-quiescent-slow-cycling-cells-via-reducing-quiescence-depth-by-natural-compounds-purified-from-ganoderma-lucidum
#10
Jian Dai, Matthew A Miller, Nicholas J Everetts, Xia Wang, Peng Li, Ye Li, Jian-Hua Xu, Guang Yao
The medical mushroom Ganoderma lucidum has long been used in traditional Chinese medicine and shown effective in the treatment of many diseases including cancer. Here we studied the cytotoxic effects of two natural compounds purified from Ganoderma lucidum, ergosterol peroxide and ganodermanondiol. We found that these two compounds exhibited cytotoxicity not only against fast proliferating cells, but on quiescent, slow-cycling cells. Using a fibroblast cell-quiescence model, we found that the cytotoxicity on quiescent cells was due to induced apoptosis, and was associated with a shallower quiescent state in compound-treated cells, resultant from the increased basal activity of an Rb-E2F bistable switch that controls quiescence exit...
January 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28097652/mdm4-is-a-rational-target-for-treating-breast-cancers-with-mutant-p53
#11
Panimaya Jeffreena Miranda, Daniel Buckley, Dinesh Raghu, Jia-Min B Pang, Elena A Takano, Reshma Vijayakumaran, Amina F A S Teunisse, Atara Posner, Tahlia Procter, Marco J Herold, Cristina Gamell, Jean-Christophe Marine, Stephen B Fox, Aart Jochemsen, Sue Haupt, Ygal Haupt
Mutation of the key tumour suppressor p53 defines a transition in the progression toward aggressive and metastatic breast cancer (BC) with the poorest outcome. Specifically, p53 mutation frequency exceeds 50% in Triple Negative BC (TNBC). Key regulators of mutant p53 that facilitate its oncogenic functions are potential therapeutic targets. We report here that the MDM4 protein is frequently abundant in the context of mutant p53 in basal-like BC samples. Importantly, we show that MDM4 plays a critical role in the proliferation of these BC cells...
January 18, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28096336/%C3%AE-catenin-haploinsufficiency-promotes-mammary-tumorigenesis-in-an-erbb2-positive-basal-breast-cancer-model
#12
Bui Tung, Babette Schade, Robert D Cardiff, Olulanu H Aina, Virginie Sanguin-Gendreau, William J Muller
Aberrant activation of β-catenin through its activity as a transcription factor has been observed in a large proportion of human malignancies. Despite the improved understanding of the β-catenin signaling pathway over the past three decades, attempts to develop therapies targeting β-catenin remain challenging, and none of these targeted therapies have advanced to the clinic. In this study, we show that part of the challenge in antagonizing β-catenin is caused by its dual functionality as a cell adhesion molecule and a signaling molecule...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28096238/activation-of-trpa1-channel-by-antibacterial-agent-triclosan-induces-vegf-secretion-in-human-prostate-cancer-stromal-cells
#13
Sandra Derouiche, Pascal Mariot, Marine Warnier, Eric Vancauwenberghe, Gabriel Bidaux, Pierre Gosset, Brigitte Mauroy, Jean-Louis Bonnal, Christian Slomianny, Philippe Delcourt, Etienne Dewailly, Natalia Prevarskaya, Morad Roudbaraki
Accruing evidence indicates that exposure to environmental compounds may adversely impact human health and promote carcinogenesis. Triclosan (TCS), an antimicrobial agent widely used as a preservative in personal care products, has been shown to act as an endocrine disruptor in hormone-dependent tissues. Here we demonstrate a new molecular mechanism by which TCS stimulates the secretion by human prostate cancer stromal cells of Vascular Endothelial Growth Factor (VEGF), a factor known to promote tumour growth...
January 17, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28092772/the-expression-of-endothelin-1-in-chronic-lymphocytic-leukemia-is-controlled-by-epigenetic-mechanisms-and-extracellular-stimuli
#14
Silvia Martinelli, Rossana Maffei, Stefania Fiorcari, Chiara Quadrelli, Patrizia Zucchini, Stefania Benatti, Leonardo Potenza, Mario Luppi, Roberto Marasca
Endothelin-1 (ET-1) is a hormone peptide widely expressed and is involved in several biological processes, important not only for normal cell function but also for tumor development, including cell proliferation, invasion, metastasis, angiogenesis and osteogenesis. In accordance, ET-1 was already shown to contribute to the growth and progression of many different solid cancers. We recently demonstrated that ET-1 has a role in the pathogenesis of chronic lymphocytic leukemia (CLL) where it is abnormally expressed...
December 30, 2016: Leukemia Research
https://www.readbyqxmd.com/read/28087714/dlg5-connects-cell-polarity-and-hippo-signaling-protein-networks-by-linking-par-1-with-mst1-2
#15
Julian Kwan, Anna Sczaniecka, Emad Heidary Arash, Liem Nguyen, Chia-Chun Chen, Srdjana Ratkovic, Olga Klezovitch, Liliana Attisano, Helen McNeill, Andrew Emili, Valeri Vasioukhin
Disruption of apical-basal polarity is implicated in developmental disorders and cancer; however, the mechanisms connecting cell polarity proteins with intracellular signaling pathways are largely unknown. We determined previously that membrane-associated guanylate kinase (MAGUK) protein discs large homolog 5 (DLG5) functions in cell polarity and regulates cellular proliferation and differentiation via undefined mechanisms. We report here that DLG5 functions as an evolutionarily conserved scaffold and negative regulator of Hippo signaling, which controls organ size through the modulation of cell proliferation and differentiation...
December 15, 2016: Genes & Development
https://www.readbyqxmd.com/read/28087292/loss-of-cd28-within-cd4-t-cell-subsets-from-cervical-cancer-patients-is-accompanied-by-the-acquisition-of-intracellular-perforin-and-is-further-enhanced-by-nkg2d-expression
#16
Marta Escarra-Senmarti, Miriam Ruth Bueno-Topete, Luis Felipe Jave-Suarez, Eduardo Gomez-Bañuelos, Jorge Gutierrez-Franco, Natali Vega-Magaña, Adriana Aguilar-Lemarroy, Ana Laura Pereira-Suarez, Jesse Haramati, Susana Del Toro-Arreola
CD28 is well characterized as an essential co-stimulatory receptor critical for activation, proliferation and survival processes in CD4(+) T cells. Populations of CD4(+)CD28(null) T cells, with apparently contradictory physiological roles, have recently been reported, along with the co-expression of the NK activating receptor NKG2D, in autoimmune diseases and chronic viral inflammation. Paradoxically, studies in cancer suggest that an expanded CD4(+)NKG2D(+) population may be armed with immunosuppressive properties...
January 10, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28087048/-characteristics-and-risk-factors-for-recurrence-of-cutaneous-squamous-cell-carcinoma-with-conventional-surgery-and-surgery-with-delayed-intraoperative-margin-assessment
#17
Judith Domínguez-Cherit, Georgina Rodríguez-Gutiérrez, Verónica Narváez Rosales, Sonia Toussaint Caire, Verónica Fonte Avalos
BACKGROUND: Non-melanoma skin cancer includes basal cell carcinoma and squamous cell carcinoma (SCC). Basal cell carcinoma is the most common and least aggressive but in a low percentage of cases, despite appropriate wide surgical margins, it can be aggressive, producing local invasion, recurrences and distance metastasis. SCC has a more aggressive behaviour invading first the skin, the lymph nodes and less frequently produces distance metastasis OBJECTIVE: To identify the characteristics of recurrent SCC and frequency of new SCC after conventional surgical and primary closure or closure delayed until a histological reporting of tumour-free surgical margins, in order to achieve a better surgical option, in our Mexican population...
January 10, 2017: Cirugia y Cirujanos
https://www.readbyqxmd.com/read/28081215/genome-wide-association-studies-of-multiple-keratinocyte-cancers
#18
Luba M Pardo, Wen-Qing Li, Shih-Jen Hwang, Joris A C Verkouteren, Albert Hofman, André G Uitterlinden, Peter Kraft, Constance Turman, Jiali Han, Eunyoung Cho, Joanne M Murabito, Daniel Levy, Abrar A Qureshi, Tamar Nijsten
There is strong evidence for a role of environmental risk factors involved in susceptibility to develop multiple keratinocyte cancers (mKCs), but whether genes are also involved in mKCs susceptibility has not been thoroughly investigated. We investigated whether single nucleotide polymorphisms (SNPs) are associated with susceptibility for mKCs. A genome-wide association study (GWAS) of 1,666 cases with mKCs and 1,950 cases with single KC (sKCs; controls) from Harvard cohorts (the Nurses' Health Study [NHS], NHS II, and the Health Professionals Follow-Up Study) and the Framingham Heart Study was carried-out using over 8 million SNPs (stage-1)...
2017: PloS One
https://www.readbyqxmd.com/read/28079291/prognostic-value-of-pd-l1-in-breast-cancer-a-meta-analysis
#19
Changjun Wang, Hanjiang Zhu, Yidong Zhou, Feng Mao, Yan Lin, Bo Pan, Xiaohui Zhang, Qianqian Xu, Xin Huang, Qiang Sun
Programmed cell death 1 ligand 1 (PD-L1) is a promising therapeutic target for cancer immunotherapy. However, the correlation between PD-L1 and breast cancer survival remains unclear. Here, we present the first meta-analysis to investigate the prognostic value of PD-L1 in breast cancer. We searched Pubmed, Embase, and Cochrane Central Register of Controlled Trials databases for relevant studies evaluating PD-L1 expression and breast cancer survival. Fixed- and random-effect meta-analyses were conducted based on heterogeneity of included studies...
January 12, 2017: Breast Journal
https://www.readbyqxmd.com/read/28077797/repression-of-fyn-related-kinase-in-breast-cancer-cells-is-associated-with-promoter-site-specific-cpg-methylation
#20
Edward T Bagu, Sayem Miah, Chenlu Dai, Travis Spriggs, Yetunde Ogunbolude, Erika Beaton, Michelle Sanders, Raghuveera K Goel, Keith Bonham, Kiven E Lukong
The triple-negative breast cancer subtype is highly aggressive and has no defined therapeutic target. Fyn-related kinase (FRK) is a non-receptor tyrosine kinase, reported to be downregulated in breast cancer and gliomas, where it is suggested to have tumor suppressor activity. We examined the expression profile of FRK in a panel of 40 breast cancer cells representing all the major subtypes, as well as in 4 non-malignant mammary epithelial cell lines. We found that FRK expression was significantly repressed in a proportion of basal B breast cancer cell lines...
January 6, 2017: Oncotarget
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