Read by QxMD icon Read

Breast cancer decitabine

Jia Yu, Bo Qin, Ann M Moyer, Somaira Nowsheen, Tongzheng Liu, Sisi Qin, Yongxian Zhuang, Duan Liu, Shijia W Lu, Krishna R Kalari, Daniel W Visscher, John A Copland, Sarah A McLaughlin, Alvaro Moreno-Aspitia, Donald W Northfelt, Richard J Gray, Zhenkun Lou, Vera J Suman, Richard Weinshilboum, Judy C Boughey, Matthew P Goetz, Liewei Wang
Triple-negative breast cancer (TNBC) is a heterogeneous disease with poor prognosis that lacks targeted therapies, especially in patients with chemotherapy-resistant disease. Since DNA methylation-induced silencing of tumor suppressors is common in cancer, reversal of promoter DNA hypermethylation by 5-aza-2'-deoxycytidine (decitabine), an FDA-approved DNA methyltransferase (DNMT) inhibitor, has proven effective in treating hematological neoplasms. However, its antitumor effect varies in solid tumors, stressing the importance of identifying biomarkers predictive of therapeutic response...
April 30, 2018: Journal of Clinical Investigation
Mohammad Sultan, Dejan Vidovic, Arianne S Paine, Thomas T Huynh, Krysta M Coyle, Margaret L Thomas, Brianne M Cruickshank, Cheryl A Dean, Derek R Clements, Youra Kim, Kristin Lee, Shashi A Gujar, Ian C Weaver, Paola Marcato
Avoiding detection and destruction by immune cells is key for tumor initiation and progression. The important role of cancer stem cells (CSC) in tumor initiation has been well established, yet their ability to evade immune detection and targeting is only partly understood. To investigate the ability of breast CSCs to evade immune detection we identified a highly tumorigenic population in a spontaneous murine mammary tumor based on increased aldehyde dehydrogenase (ALDH) activity. We performed tumor growth studies in immunocompetent and immunocompromised mice...
January 17, 2018: Stem Cells
Ewa Maria Nowak, Marta Poczęta, Dominik Bieg, Ilona Bednarek
OBJECTIVES: Downregulation of DIRAS3 (DIRAS family, GTP-binding Ras-like 3) is related to ovarian and breast cancer progression. A possible mechanism that silences this gene is the promoter region DNA methylation. The potential reversibility of this epigenetic mechanism makes it more attractive candidate for new mode of cancer treatment. DIRAS3 regulates cell cycle, tumor dormancy and inhibits cancer cell growth and motility, all of which may indirectly depend on interaction with STAT3 (Signal Transducer and Activator of Transcription 3) classified as a potential oncogene...
2017: Ginekologia Polska
Xuexiao Wang, Jiali Wang, Yunlong Jia, Yu Wang, Xiaonan Han, Yuqing Duan, Wei Lv, Ming Ma, Lihua Liu
Bridging integrator-1 (Bin1), as a tumor suppressor, is frequently attenuated or even abolished in multiple primary cancers. A reduced expression of Bin1 caused by DNA methylation, has been reported in breast and prostate cancers. However, the methylation status of Bin1 and potent biological functions in esophageal squamous cell carcinoma (ESCC) remain unclear. In a previous study, we showed that the Bin1 expression was low in ESCC tissues. Herein, we further characterized this mechanism, confirming that gene hypermethylation was significantly correlated with the aberrant attenuation of Bin1...
March 21, 2017: Oncotarget
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...
February 2017: Molecular Cancer Research: MCR
Paola Maroni, Emanuela Matteucci, Paola Bendinelli, Maria Alfonsina Desiderio
Epigenetic mechanisms influence molecular patterns important for the bone-metastatic process, and here we highlight the role of WW-domain containing oxidoreductase (Wwox). The tumor-suppressor Wwox lacks in almost all cancer types; the variable expression in osteosarcomas is related to lung-metastasis formation, and exogenous Wwox destabilizes HIF-1α (subunit of Hypoxia inducible Factor-1, HIF-1) affecting aerobic glycolysis. Our recent studies show critical functions of Wwox present in 1833-osteotropic clone, in the corresponding xenograft model, and in human bone metastasis from breast carcinoma...
January 1, 2017: International Journal of Molecular Sciences
Ameet K Mishra, Annelie Abrahamsson, Charlotta Dabrosin
The estrogen receptor-alpha (ERα) is used as a predictive marker for anti-estrogen therapy in breast cancer patients. In addition to aromatase inhibitors, ERα can be targeted at the receptor level using the receptor modulator tamoxifen or by the pure anti-estrogen fulvestrant. The role of the second ER, ER-beta (ERβ), as a therapeutic target or prognostic marker in breast cancer is still elusive. Hitherto, it is not known if ERα+/ERβ+ breast cancers would benefit from a treatment strategy combining tamoxifen and fulvestrant or if fulvestrant exert any therapeutic effects in ERα-/ERβ+ breast cancer...
August 30, 2016: Oncotarget
Krista P Terracina, Laura J Graham, Kyle K Payne, Masoud H Manjili, Annabel Baek, Sheela R Damle, Harry D Bear
Adoptive T cell immunotherapy is a promising approach to cancer treatment that currently has limited clinical applications. DNA methyltransferase inhibitors (DNAMTi) have known potential to affect the immune system through multiple mechanisms that could enhance the cytotoxic T cell responses, including: upregulation of tumor antigen expression, increased MHC class I expression, and blunting of myeloid derived suppressor cells (MDSCs) expansion. In this study, we have investigated the effect of combining the DNAMTi, decitabine, with adoptive T cell immunotherapy in the murine 4T1 mammary carcinoma model...
September 2016: Cancer Immunology, Immunotherapy: CII
Mélodie Grandin, Pauline Mathot, Guillaume Devailly, Yannick Bidet, Akram Ghantous, Clementine Favrot, Benjamin Gibert, Nicolas Gadot, Isabelle Puisieux, Zdenko Herceg, Jean-Guy Delcros, Agnès Bernet, Patrick Mehlen, Robert Dante
In a number of human cancers, NTN1 upregulation inhibits apoptosis induced by its so-called dependence receptors DCC and UNC5H, thus promoting tumor progression. In other cancers however, the selective inhibition of this dependence receptor death pathway relies on the silencing of pro-apoptotic effector proteins. We show here that a substantial fraction of human breast tumors exhibits simultaneous DNA methylation-dependent loss of expression of NTN1 and of DAPK1, a serine threonine kinase known to transduce the netrin-1 dependence receptor pro-apoptotic pathway...
August 2016: EMBO Molecular Medicine
Jessica N Haladyna, Taylor Pastuer, Simone S Riedel, Anne-Laure Perraud, Kathrin M Bernt
Transient potential receptor melastatin-2 (TRPM2) is a nonselective cationic, Ca(2+)-permeable transmembrane pore that is preferentially expressed in cells of the myeloid lineage and modulates signaling pathways converging into NF-kB. This is of potential interest for acute myeloid leukemia (AML) therapy, as NF-κB signaling is emerging as a key pathway, mediating drug resistance and leukemia-initiating cell survival in AML. Inhibition of NF-κB signaling has been found to be synergistic with chemotherapy. TRPM2 is overexpressed in AML compared with normal bone marrow, with the highest levels in the FAB M3-6 subtypes...
July 2016: Experimental Hematology
Michelle L Stewart, Pablo Tamayo, Andrew J Wilson, Stephanie Wang, Yun Min Chang, Jong W Kim, Dineo Khabele, Alykhan F Shamji, Stuart L Schreiber
Decitabine, a cancer therapeutic that inhibits DNA methylation, produces variable antitumor response rates in patients with solid tumors that might be leveraged clinically with identification of a predictive biomarker. In this study, we profiled the response of human ovarian, melanoma, and breast cancer cells treated with decitabine, finding that RAS/MEK/ERK pathway activation and DNMT1 expression correlated with cytotoxic activity. Further, we showed that KRAS genomic status predicted decitabine sensitivity in low-grade and high-grade serous ovarian cancer cells...
July 15, 2015: Cancer Research
Dong-Xu He, Yu-Dong Xia, Xiao-Ting Gu, Jian Jin, Xin Ma
Although chemotherapy is widely used to treat human cancers, most chemotherapeutic agents only benefit a small fraction of patients because of the heterogeneity of cancers. Therefore, identifying of the sensitivity of cancers toward various chemotherapies would be important for choosing of chemotherapeutic regime. In this study, a 23-gene chemoresistance signature was developed from chemoresistant breast cancers. Functions of the genes in the signature were related with transcription and translation. The signature was indicative of chemoresistance and associated with poor prognosis in multiple chemotherapeutic agents and cancer types...
January 2015: Journal of Pharmaceutical and Biomedical Analysis
Shi-Yong Li, Rong Sun, Hong-Xia Wang, Song Shen, Yang Liu, Xiao-Jiao Du, Yan-Hua Zhu, Wang Jun
Aberrant DNA hypermethylation is critical in the regulation of renewal and maintenance of cancer stem cells (CSCs), which represent targets for carcinogenic initiation by chemical and environmental agents. The administration of decitabine (DAC), which is a DNA hypermethylation inhibitor, is an attractive approach to enhancing the chemotherapeutic response and overcoming drug resistance by CSCs. In this study, we investigated whether low-dose DAC encapsulated in nanoparticles could be used to sensitize bulk breast cancer cells and CSCs to chemotherapy...
May 10, 2015: Journal of Controlled Release: Official Journal of the Controlled Release Society
Hong-Xue Wu, Shi-Lun Tong, Chong Wu, Wei-Xing Wang
OBJECTIVES: To explore HtrA1 gene expression and its regulation in human gastric cancers. METHODS: The HtrA1 mRNA levels were examined by QPCR analysis and confirmed its expression with Northern blot analysis. The HtrA1 protein levels in all six gastric epithelial cell lines were investigated by Western blot analysis. Gene copy number was accessed and then sequenced the coding region from each mRNA in all six cell lines. The HtrA1 promoter region DNA methylation status was detected by using bisulfite sequencing analysis...
October 2014: Asian Pacific Journal of Tropical Medicine
Lei Cao, Hua Gao, Ping Li, Songbai Gui, Yazhuo Zhang
Although an antiestrogen treatment for estrogen-dependent diseases, such as breast cancers, has been reported, the effect of this endocrine therapy on prolactinomas and its possible mechanism are unclear. This study investigates the antitumor effect of fulvestrant, which is a new estrogen receptor antagonist, on rat prolactinoma MMQ cells and the possible roles of the Wnt/β-catenin signaling pathway that is involved in this antitumor effect. To investigate the antitumor effect of fulvestrant, the effects of exposure to gradient doses of fulvestrant (0, 0...
June 2014: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Sahra Borges, Heike Döppler, Edith A Perez, Cathy A Andorfer, Zhifu Sun, Panos Z Anastasiadis, E Thompson, Xochiquetzal J Geiger, Peter Storz
INTRODUCTION: DNA methylation-induced silencing of genes encoding tumor suppressors is common in many types of cancer, but little is known about how such epigenetic silencing can contribute to tumor metastasis. The PRKD1 gene encodes protein kinase D1 (PKD1), a serine/threonine kinase that is expressed in cells of the normal mammary gland, where it maintains the epithelial phenotype by preventing epithelial-to-mesenchymal transition. METHODS: The status of PRKD1 promoter methylation was analyzed by reduced representation bisulfite deep sequencing, methylation-specific PCR (MSP-PCR) and in situ MSP-PCR in invasive and noninvasive breast cancer lines, as well as in humans in 34 cases of "normal" tissue, 22 cases of ductal carcinoma in situ, 22 cases of estrogen receptor positive, HER2-negative (ER+/HER2-) invasive lobular carcinoma, 43 cases of ER+/HER2- invasive ductal carcinoma (IDC), 93 cases of HER2+ IDC and 96 cases of triple-negative IDC...
2013: Breast Cancer Research: BCR
Francescopaolo Di Cello, Leslie Cope, Huili Li, Jana Jeschke, Wei Wang, Stephen B Baylin, Cynthia A Zahnow
Downregulation of the tight junction protein claudin 1 is a frequent event in breast cancer and is associated with recurrence, metastasis, and reduced survival, suggesting a tumor suppressor role for this protein. Tumor suppressor genes are often epigenetically silenced in cancer. Downregulation of claudin 1 via DNA promoter methylation may thus be an important determinant in breast cancer development and progression. To investigate if silencing of claudin 1 has an epigenetic etiology in breast cancer we compared gene expression and methylation data from 217 breast cancer samples and 40 matched normal samples available through the Cancer Genome Atlas (TCGA)...
2013: PloS One
Kareem I Batarseh
In a previous work, the author has investigated the antimicrobial and cytotoxic properties of tartaric and glutamic acids silver(I) chelates. In a following work, the author has reported on the in vitro cytotoxicity and the mechanism of action of a silver(I) tartaric acid chelate synthesized by the author given the title name Aliargentumycine (AAgM) on hematopoietic malignancies. The in vitro antineoplastic activities of AAgM on solid human breast ductal carcinoma (T- 47D) and disseminated T-cell acute lymphoblastic leukemia (Jurkat) cell lines, its mechanism of action and its structural properties were investigated here...
2013: Current Medicinal Chemistry
Sivakumar Vijayaraghavalu, Vinod Labhasetwar
DNA methyltransferase 1 (DNMT1) promotes DNA methylation to maintain cancer drug resistance. The epigenetic drug, decitabine (DAC) is a potent hypomethylating agent, but its effect is transient because of its instability. We tested the efficacy of DAC-loaded nanogels in doxorubicin-resistant breast cancer cells, DAC-resistant melanoma cells, and leukemia cells. DAC in nanogel sustained DNMT1 depletion, prolonged cell arrest in the G2/M cell-cycle phase, and significantly enhanced antiproliferative effect of DAC...
April 30, 2013: Cancer Letters
Sivakumar Vijayaraghavalu, Josephine Kamtai Dermawan, Venugopalan Cheriyath, Vinod Labhasetwar
Epigenetic alterations such as aberrant DNA methylation and histone modifications contribute substantially to both the cause and maintenance of drug resistance. These epigenetic changes lead to silencing of tumor suppressor genes involved in key DNA damage-response pathways, making drug-resistant cancer cells nonresponsive to conventional anticancer drug therapies. Our hypothesis is that treating drug-resistant cells with epigenetic drugs could restore the sensitivity to anticancer drugs by reactivating previously silenced genes...
January 7, 2013: Molecular Pharmaceutics
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"