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https://www.readbyqxmd.com/read/29138265/targeted-delivery-of-stat-3-modulator-to-breast-cancer-stem-like-cells-down-regulates-a-series-of-stem-ness-genes
#1
Santosh K Misra, Arun De, Dipanjan Pan
Cancer stem cells are known to be controlled by pathways that are dormant in normal adult cells, e.g. PTEN, which is a negative regulator of transcription factor STAT3. STAT3 regulates genes that are involved in stem cell self-renewal and thus represents a novel therapeutic target of enormous clinical significance. Studies on breast cancer stem cells (BCSCs) have been also significantly correlated with STATs. We describe here for the first time a novel strategy to selectively target CSCs and to induce downregulation of STAT3 downstream target genes reducing expression of series of 'stem-ness genes' in treated tumors...
November 14, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29137436/tumor-biopsy-stratification-based-on-mtor-pathway-activity-and-functional-mutations-in-the-upstream-genes-pik3ca-and-pten
#2
Jean-François Laes, Sebastien Sauvage, Gregori Ghitti
The mechanistic target of the rapamycin (mTOR) pathway is frequently activated in human cancers. Our objective was to evaluate relationships between mTOR-pathway activity and functional mutations in the upstream genes PIK3CA and PTEN in solid-tumor biopsies from a broad selection of cancer types. Formalin-fixed paraffin-embedded (FFPE) tumor samples were analyzed by immunohistochemistry (IHC) and next-generation sequencing (NGS). TOR-pathway activation was identified by expression (by IHC) of the downstream effector p-4E-BP1...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137351/microrna-200-associated-with-metastatic-breast-cancer-promotes-traits-of-mammary-luminal-progenitor-cells
#3
Lourdes Sánchez-Cid, Mònica Pons, Juan José Lozano, Nuria Rubio, Marta Guerra-Rebollo, Aroa Soriano, Laia Paris-Coderch, Miquel F Segura, Raquel Fueyo, Judit Arguimbau, Erika Zodda, Raquel Bermudo, Immaculada Alonso, Xavier Caparrós, Marta Cascante, Arash Rafii, Yibin Kang, Marian Martínez-Balbás, Stephen J Weiss, Jerónimo Blanco, Montserrat Muñoz, Pedro L Fernández, Timothy M Thomson
MicroRNAs are critical regulators of gene networks in normal and abnormal biological processes. Focusing on invasive ductal breast cancer (IDC), we have found dysregulated expression in tumor samples of several microRNAs, including the miR-200 family, along progression from primary tumors to distant metastases, further reflected in higher blood levels of miR-200b and miR-7 in IDC patients with regional or distant metastases relative to patients with primary node-negative tumors. Forced expression of miR-200s in MCF10CA1h mammary cells induced an enhanced epithelial program, aldehyde dehydrogenase (ALDH) activity, mammosphere growth and ability to form branched tubuloalveolar structures while promoting orthotopic tumor growth and lung colonization in vivo...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136733/-exploratory-study-of-circulating-tumor-dna-detection-in-early-breast-cancer-an-analysis-of-75-next-generation-sequencing-results
#4
B Zhou, L Xin, L Xu, Y H Liu, M M Zhang, R L Jing, X Y Liang, S B Cao
Objective: To explore the utility of circulating tumor DNA detection in early breast cancer by using next-generation sequencing. Methods: This exploratory study of circulating tumor DNA detection is for early invasive breast cancer patients treated in Breast Disease Center, Peking University First Hospital from December 2015 to July 2016. Plasma samples were collected and were used to isolate plasma cell-free DNA.Exons or hotspots of 247 cancer related genes were sequenced by next-generation sequencing. Mutations and their correlation with clinic-pathological factors were analyzed...
November 1, 2017: Zhonghua Wai Ke za Zhi [Chinese Journal of Surgery]
https://www.readbyqxmd.com/read/29133799/hit-and-run-epigenetic-editing-prevents-senescence-entry-in-primary-breast-cells-from-healthy-donors
#5
Emily A Saunderson, Peter Stepper, Jennifer J Gomm, Lily Hoa, Adrienne Morgan, Michael D Allen, J Louise Jones, John G Gribben, Tomasz P Jurkowski, Gabriella Ficz
Aberrant promoter DNA hypermethylation is a hallmark of cancer; however, whether this is sufficient to drive cellular transformation is not clear. To investigate this question, we use a CRISPR-dCas9 epigenetic editing tool, where an inactive form of Cas9 is fused to DNA methyltransferase effectors. Using this system, here we show simultaneous de novo DNA methylation of genes commonly methylated in cancer, CDKN2A, RASSF1, HIC1 and PTEN in primary breast cells isolated from healthy human breast tissue. We find that promoter methylation is maintained in this system, even in the absence of the fusion construct, and this prevents cells from engaging senescence arrest...
November 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29130495/matrine-reversed-multidrug-resistance-of-breast-cancer-mcf-7-adr-cells-through-pi3k-akt-signal-pathway
#6
Bing-Gang Zhou, Chang-Sheng Wei, Song Zhang, Zhi Zhang, Huan-Min Gao
Matrine is an alkaloid extracted from a Chinese herb Sophora flavescens Ait, and has been used clinically for breast cancer with marked therapeutic efficacy in China. However, the mechanism has not been well known. Thus the present study was to explore if Matrine reverse multidrug resistance for breast cancer cells though regulating PI3K/AKT signal pathway. Methyl thiazolyl tetrazolium (MTT) assay was used to detect the inhibitory action; Annexin V to detect apoptosis; Fluorospectrophotometry to examine intracellular adriamycin (ADR) accumulation and Western-blot to label the proteins of P-glycoprotein(P-gp), MRP1, PTEN, p-AKT, Bcl-2, Bax and Caspase-3...
November 11, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29127587/copanlisib-first-global-approval
#7
Anthony Markham
Bayer are developing copanlisib (Aliqopa™)-a pan-class I phosphoinositide 3-kinase (PI3K) inhibitor-as a treatment for various haematological and solid malignancies. The US FDA has granted copanlisib accelerated approval for the treatment of adults with relapsed follicular lymphoma who have received at least two prior systemic therapies based on the results of a phase II trial. Phase III trials are underway evaluating copanlisib as treatment for relapsed/refractory diffuse large B-cell lymphoma and in combination with rituximab or rituximab-based chemotherapy or standard immunochemotherapy in patients with relapsed indolent B-cell non-Hodgkin's lymphoma...
November 10, 2017: Drugs
https://www.readbyqxmd.com/read/29115608/microrna%C3%A2-27a-promotes-tumorigenesis-via-targeting-akt-in-triple-negative-breast-cancer
#8
Jing Wu, Zhihui Sun, Huijie Sun, Yanhua Li
Altered microRNA (miRNA/miR) expression regulates tumor development and progression in triple‑negative breast cancer (TNBC). The present study examined the effect of miR‑27a on proliferation, migration and invasion of TNBC cells in vitro and in vivo. An MTT assay was performed to examine the proliferation of MDA‑MB‑231 and MDA‑MB‑468 breast cancer cells with either overexpression of miR‑27a or downregulation of miR‑27a, in the presence or absence of radiation. The migratory and invasive abilities of MDA‑MB‑231 and MDA‑MB‑468 breast cancer cells were assessed by Transwell migration and Matrigel invasion assays...
October 26, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29110152/low-pten-levels-and-pik3ca-mutations-predict-resistance-to-neoadjuvant-lapatinib-and-trastuzumab-without-chemotherapy-in-patients-with-her2-over-expressing-breast-cancer
#9
Mothaffar F Rimawi, Carmine De Angelis, Alejandro Contreras, Fresia Pareja, Felipe C Geyer, Kathleen A Burke, Sabrina Herrera, Tao Wang, Ingrid A Mayer, Andres Forero, Rita Nanda, Matthew P Goetz, Jenny C Chang, Ian E Krop, Antonio C Wolff, Anne C Pavlick, Suzanne A W Fuqua, Carolina Gutierrez, Susan G Hilsenbeck, Marilyn M Li, Britta Weigelt, Jorge S Reis-Filho, C Kent Osborne, Rachel Schiff
PURPOSE: Aberrant activation of the PI3K pathway has been implicated in resistance to HER2-targeted therapy, but results of clinical trials are confounded by the co-administration of chemotherapy. We investigated the effect of perturbations of this pathway in breast cancers from patients treated with neoadjuvant anti-HER2-targeted therapy without chemotherapy. PATIENTS AND METHODS: Baseline tumor samples from patients with HER2-positive breast cancer enrolled in TBCRC006 (NCT00548184), a 12-week neoadjuvant clinical trial with lapatinib plus trastuzumab [plus endocrine therapy for estrogen receptor (ER)-positive tumors], were assessed for PTEN status by immunohistochemistry and PIK3CA mutations by sequencing...
November 7, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29103666/identification-of-single-nucleotide-polymorphisms-of-the-pi3k-akt-mtor-pathway-as-a-risk-factor-of-central-nervous-system-metastasis-in-metastatic-breast-cancer
#10
Emilie Le Rhun, Nicolas Bertrand, Aurélie Dumont, Emmanuelle Tresch, Marie-Cécile Le Deley, Audrey Mailliez, Matthias Preusser, Michael Weller, Françoise Revillion, Jacques Bonneterre
INTRODUCTION: The PI3K-AKT-mTOR pathway may be involved in the development of central nervous system (CNS) metastasis from breast cancer. Accordingly, herein we explored whether single nucleotide polymorphisms (SNPs) of this pathway are associated with altered risk of CNS metastasis formation in metastatic breast cancer patients. METHODS: The GENEOM study (NCT00959556) included blood sample collection from breast cancer patients treated in the neoadjuvant, adjuvant or metastatic setting...
November 2, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/29076877/the-role-of-molecular-testing-in-the-differential-diagnosis-of-salivary-gland-carcinomas
#11
Alena Skálová, Göran Stenman, Roderick H W Simpson, Henrik Hellquist, David Slouka, Tomas Svoboda, Justin A Bishop, Jennifer L Hunt, Ken-Ichi Nibu, Alessandra Rinaldo, Vincent Vander Poorten, Kenneth O Devaney, Petr Steiner, Alfio Ferlito
Salivary gland neoplasms are a morphologically heterogenous group of lesions that are often diagnostically challenging. In recent years, considerable progress in salivary gland taxonomy has been reached by the discovery of tumor type-specific fusion oncogenes generated by chromosome translocations. This review describes the clinicopathologic features of a selected group of salivary gland carcinomas with a focus on their distinctive genomic characteristics. Mammary analog secretory carcinoma is a recently described entity characterized by a t(12;15)(p13;q25) translocation resulting in an ETV6-NTRK3 fusion...
October 26, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29059158/raf-inhibitor-ly3009120-sensitizes-ras-or-braf-mutant-cancer-to-cdk4-6-inhibition-by-abemaciclib-via-superior-inhibition-of-phospho-rb-and-suppression-of-cyclin-d1
#12
S-H Chen, X Gong, Y Zhang, R D Van Horn, T Yin, L Huber, T F Burke, J Manro, P W Iversen, W Wu, S V Bhagwat, R P Beckmann, R V Tiu, S G Buchanan, S-B Peng
KRAS, NRAS and BRAF mutations are among the most important oncogenic drivers in many major cancer types, such as melanoma, lung, colorectal and pancreatic cancer. There is currently no effective therapy for the treatment of RAS mutant cancers. LY3009120, a pan-RAF and RAF dimer inhibitor advanced to clinical study has been shown to inhibit both RAS and BRAF mutant cell proliferation in vitro and xenograft tumor growth in vivo. Abemaciclib, a CDK4/6-selective inhibitor, is currently in phase III studies for ER-positive breast cancer and KRAS mutant lung cancer...
October 23, 2017: Oncogene
https://www.readbyqxmd.com/read/29057879/deletion-of-3p13-14-locus-spanning-foxp1-to-shq1-cooperates-with-pten-loss-in-prostate-oncogenesis
#13
Haley Hieronymus, Phillip J Iaquinta, John Wongvipat, Anuradha Gopalan, Rajmohan Murali, Ninghui Mao, Brett S Carver, Charles L Sawyers
A multigenic locus at 3p13-14, spanning FOXP1 to SHQ1, is commonly deleted in prostate cancer and lost broadly in a range of cancers but has unknown significance to oncogenesis or prognosis. Here, we report that FOXP1-SHQ1 deletion cooperates with PTEN loss to accelerate prostate oncogenesis and that loss of component genes correlates with prostate, breast, and head and neck cancer recurrence. We demonstrate that Foxp1-Shq1 deletion accelerates prostate tumorigenesis in mice in combination with Pten loss, consistent with the association of FOXP1-SHQ1 and PTEN loss observed in human cancers...
October 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/29056325/pten-regulates-pi-3-4-p2-signaling-downstream-of-class-i-pi3k
#14
Mouhannad Malek, Anna Kielkowska, Tamara Chessa, Karen E Anderson, David Barneda, Pınar Pir, Hiroki Nakanishi, Satoshi Eguchi, Atsushi Koizumi, Junko Sasaki, Véronique Juvin, Vladimir Y Kiselev, Izabella Niewczas, Alexander Gray, Alexandre Valayer, Dominik Spensberger, Marine Imbert, Sergio Felisbino, Tomonori Habuchi, Soren Beinke, Sabina Cosulich, Nicolas Le Novère, Takehiko Sasaki, Jonathan Clark, Phillip T Hawkins, Len R Stephens
The PI3K signaling pathway regulates cell growth and movement and is heavily mutated in cancer. Class I PI3Ks synthesize the lipid messenger PI(3,4,5)P3. PI(3,4,5)P3 can be dephosphorylated by 3- or 5-phosphatases, the latter producing PI(3,4)P2. The PTEN tumor suppressor is thought to function primarily as a PI(3,4,5)P3 3-phosphatase, limiting activation of this pathway. Here we show that PTEN also functions as a PI(3,4)P2 3-phosphatase, both in vitro and in vivo. PTEN is a major PI(3,4)P2 phosphatase in Mcf10a cytosol, and loss of PTEN and INPP4B, a known PI(3,4)P2 4-phosphatase, leads to synergistic accumulation of PI(3,4)P2, which correlated with increased invadopodia in epidermal growth factor (EGF)-stimulated cells...
November 2, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29054429/surface-chemistry-induces-mitochondria-mediated-apoptosis-of-breast-cancer-cells-via-pten-pi3k-akt-signaling-pathway
#15
Jing Zhang, Li Li, Yueting Peng, Yu Chen, Xiaoying Lv, Shun Li, Xiang Qin, Hong Yang, Chunhui Wu, Yiyao Liu
Tumor cell can be significantly influenced by various chemical groups of the extracellular matrix proteins. However, the underlying molecular mechanisms involved in the interaction between cancer cells and functional groups in the extracellular matrix remain unknown. Using chemically modified surfaces with biological functional groups (CH3, NH2, OH), it was found that hydrophobic surfaces modified with CH3 and NH2 suppressed cell proliferation and induced the number of apoptotic cells. Mitochondrial dysfunction, cytochrome c release, Bax upregulation, cleaved caspase-3 and PARP, and Bcl-2 downregulation indicated that hydrophobic surfaces with CH3 and NH2 triggered the activation of intrinsic apoptotic signaling pathway...
October 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29053726/prevalence-of-deleterious-germline-variants-in-risk-genes-including-brca1-2-in-consecutive-ovarian-cancer-patients-ago-tr-1
#16
Philipp Harter, Jan Hauke, Florian Heitz, Alexander Reuss, Stefan Kommoss, Frederik Marmé, André Heimbach, Katharina Prieske, Lisa Richters, Alexander Burges, Guido Neidhardt, Nikolaus de Gregorio, Ahmed El-Balat, Felix Hilpert, Werner Meier, Rainer Kimmig, Karin Kast, Jalid Sehouli, Klaus Baumann, Christian Jackisch, Tjoung-Won Park-Simon, Lars Hanker, Sandra Kröber, Jacobus Pfisterer, Heidrun Gevensleben, Andreas Schnelzer, Dimo Dietrich, Tanja Neunhöffer, Mathias Krockenberger, Sara Y Brucker, Peter Nürnberg, Holger Thiele, Janine Altmüller, Josefin Lamla, Gabriele Elser, Andreas du Bois, Eric Hahnen, Rita Schmutzler
BACKGROUND: Identification of families at risk for ovarian cancer offers the opportunity to consider prophylactic surgery thus reducing ovarian cancer mortality. So far, identification of potentially affected families in Germany was solely performed via family history and numbers of affected family members with breast or ovarian cancer. However, neither the prevalence of deleterious variants in BRCA1/2 in ovarian cancer in Germany nor the reliability of family history as trigger for genetic counselling has ever been evaluated...
2017: PloS One
https://www.readbyqxmd.com/read/29052531/pten-expression-is-upregulated-by-a-rna-binding-protein-rbm38-via-enhancing-its-mrna-stability-in-breast-cancer
#17
Xu-Jie Zhou, Jing Wu, Liang Shi, Xiao-Xia Li, Lei Zhu, Xi Sun, Jia-Yi Qian, Ying Wang, Ji-Fu Wei, Qiang Ding
BACKGROUND: PTEN (phosphatase and tensin homolog gene on chromosome 10), a well-characterized tumor suppressor, is a key regulator of the phosphatidylinositol-3-kinase (PI3K)/AKT pathway involved in cell survival, metastasis and cell renewal. PTEN expression is closely related to the phenotype, prognosis and drug selection in breast cancer. It is mainly regulated by transcriptional and post-transcriptional modifications. RNA binding motif protein 38 (RBM38), an RNA-binding protein (RBP) and a target of P53 family, plays a crucial role in the regulation of cellular processing, especially in post-transcription regulation and gene transcription...
October 19, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29021233/divergent-activity-of-pseudogene-ptenp1-in-er-positive-and-negative-breast-cancer
#18
Synnøve Yndestad, Eilin Austreid, Kai Ove Skaftnesmo, Per Eystein Lønning, Hans P Eikesdal
Transcripts derived from the PTEN pseudogene (PTENP1) function as decoys to adsorb microRNAs (miRs) targeting the PTEN tumor suppressor for degradation, and PTENP1 upregulation is known to inhibit growth in preclinical cancer models. Here, PTENP1 3'UTR transduction influences PTEN, AKT/mTOR signaling, and tumor progression in estrogen receptor (ER)-positive and negative breast cancer cells. PTENP1 upregulation decreases PTEN gene expression in the ER-positive MCF7 and T47D human breast carcinoma cells and accelerates MCF7 tumor growth in vivo...
October 11, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28982275/bisphenol-a-initiates-excessive-premature-activation-of-primordial-follicles-in-mouse-ovaries-via-the-pten-signaling-pathway
#19
Ying Hu, Dong-Zhi Yuan, Yi Wu, Lin-Lin Yu, Liang-Zhi Xu, Li-Min Yue, Lin Liu, Wen-Ming Xu, Xiao-Yong Qiao, Ru-Jun Zeng, Zhi-Lan Yang, Wei-Yao Yin, Ya-Xian Ma, Ying Nie
The essence of primary ovarian insufficiency (POI) is the premature exhaustion of primordial follicles in the follicle pool, which is caused by the excessive premature activation of primordial follicles after birth. Bisphenol A (BPA) exposure promotes the transition of primordial follicles to primary follicles, thus the number of primordial follicles in the primordial follicle pool decreases significantly. However, the molecular mechanisms underlying abnormal follicle activation are poorly understood. Phosphatase and tensin homologue (PTEN) signal system is a negative regulator of follicle activation, which is called the brake of follicle activation...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28975625/translational-opportunities-for-broad-spectrum-natural-phytochemicals-and-targeted-agent-combinations-in-breast-cancer
#20
REVIEW
Lokesh Dalasanur Nagaprashantha, Ramesh Adhikari, Jyotsana Singhal, Shireen Chikara, Sanjay Awasthi, David Horne, Sharad Singhal
Breast Cancer (BC) prevention and therapy in the context of life-style risk factors and biological drivers is a major focus of developmental therapeutics in Oncology. Obesity, alcohol, chronic estrogen signaling and smoking have distinct BC precipitating and facilitating effects that may act alone or in combination. A spectrum of signaling events including enhanced oxidative stress and changes in estrogen-receptor (ER) dependent and independent signaling drive the progression of BC. Breast tumors modulate ERα/ERβ ratio, upregulate proliferative pathways driven by ERα and HER2 with a parallel loss and/or down-regulation of tumor suppressors like TP53 and PTEN which together impact the efficacy of therapeutic strategies and frequently lead to emergence of drug-resistance...
October 4, 2017: International Journal of Cancer. Journal International du Cancer
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