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https://www.readbyqxmd.com/read/29785153/prevalence-of-deleterious-mutations-among-patients-with-breast-cancer-referred-for-multigene-panel-testing-in-a-romanian-population
#1
Iulian Gabriel Goidescu, Gabriela Caracostea, Dan Tudor Eniu, Florin Vasile Stamatian
Aim: Multigene panel testing for Hereditary Breast and Ovarian Cancer (HBOC) using next generation sequencing is becoming more common in medical care.We report our experience regarding deleterious mutations of high and moderate-risk breast cancer genes (BRCA1/2, TP53, STK11, CDH1, PTEN, PALB2, CHEK2, ATM), as well as more recently identified cancer genes, many of which have increased risk but less well-defined penetrance. Methods: Genetic testing was performed in 130 consecutive cases with breast cancer referred to our clinic for surgical evaluation and who met the 2016 National Comprehensive Cancer Network (NCCN) criteria for genetic testing...
2018: Clujul Medical (1957)
https://www.readbyqxmd.com/read/29783106/prediction-of-the-combined-effects-of-multiple-estrogenic-chemicals-on-mcf-7-human-breast-cancer-cells-and-a-preliminary-molecular-exploration-of-the-estrogenic-proliferative-effects-and-related-gene-expression
#2
Shengwu Yuan, Chao Huang, Xiaoya Ji, Mei Ma, Kaifeng Rao, Zijian Wang
The environmental risks of environmental estrogens (EEs) are often assessed via the same mode of action in the concentration addition (CA) model, neglecting the complex combined mechanisms at the genetic level. In this study, the cell proliferation effects of estrone, 17α-ethinylestradiol, 17β-estradiol, estriol, diethylstilbestrol, estradiol valerate, bisphenol A, 4-tert-octylphenol and 4-nonylphenol were determined individually using the CCK-8 method, and the proliferation effects of a multicomponent mixture of estrogenic chemicals mixed at equipotent concentrations using a fixed-ratio design were studied using estrogen-sensitive MCF-7 cells...
May 18, 2018: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/29777149/stretching-reduces-tumor-growth-in-a-mouse-breast-cancer-model
#3
L Berrueta, J Bergholz, D Munoz, I Muskaj, G J Badger, A Shukla, H J Kim, J J Zhao, H M Langevin
There is growing interest in developing non-pharmacological treatments that could boost natural defenses against cancer and contribute to primary and secondary cancer prevention. Recent studies have shown that gentle daily stretching for 10 minutes can reduce local connective tissue inflammation and fibrosis. Because mechanical factors within the stroma can influence the tumor microenvironment, we hypothesized that stretching would reduce the growth of tumors implanted within locally stretched tissues and tested this hypothesis in a mouse orthotopic breast cancer model...
May 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29772266/pten-pdz-binding-domain-suppresses-mammary-carcinogenesis-in-the-mmtv-pymt-breast-cancer-model
#4
Mingfei Yan, Yubing Wang, Chi Wai Wong, Penelope Mei-Yu Or, Kin Lok Wong, Lisha Li, Alexander M Many, Hong Guan, Ui Soon Khoo, Andrew M Chan
Phosphatase and tension homolog (PTEN) is a potent tumor suppressor that possesses a PDZ-binding domain (PDZ-BD) at the end of its carboxyl terminus, whose functions during tumorigenesis remains unclear. Here, we crossed a mouse strain with germline deletion of PTEN PDZ-BD with MMTV-PyMT breast cancer model, and found that knockout (KO) mice display normal development of mammary glands, but have both increased breast tumorigenicity and lung metastasis. Orthotopic allograft experiments suggest the loss of PTEN PDZ-BD in breast cancer cells rather than in tumor microenvironment plays a prominent role in increasing tumor burden...
May 14, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29765551/functional-significance-of-co-occurring-mutations-in-pik3ca-and-map3k1-in-breast-cancer
#5
Alvaro Avivar-Valderas, Robert McEwen, Amir Taheri-Ghahfarokhi, Larissa S Carnevalli, Elizabeth L Hardaker, Marcello Maresca, Kevin Hudson, Elizabeth A Harrington, Francisco Cruzalegui
The PI3Kα signaling pathway is frequently hyper-activated in breast cancer (BrCa), as a result of mutations/amplifications in oncogenes (e.g. HER2 ), decreased function in tumor suppressors (e.g. PTEN ) or activating mutations in key components of the pathway. In particular, activating mutations of PIK3CA (~45%) are frequently found in luminal A BrCa samples. Genomic studies have uncovered inactivating mutations in MAP3K1 (13-20%) and MAP2K4 (~8%), two upstream kinases of the JNK apoptotic pathway in luminal A BrCa samples...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29743588/notch-1-pten-erk1-2-signaling-axis-promotes-her2-breast-cancer-cell-proliferation-and-stem-cell-survival
#6
Andrew Baker, Debra Wyatt, Maurizio Bocchetta, Jun Li, Aleksandra Filipovic, Andrew Green, Daniel S Peiffer, Suzanne Fuqua, Lucio Miele, Kathy S Albain, Clodia Osipo
Trastuzumab targets the HER2 receptor on breast cancer cells to attenuate HER2-driven tumor growth. However, resistance to trastuzumab-based therapy remains a major clinical problem for women with HER2+ breast cancer. Breast cancer stem cells (BCSCs) are suggested to be responsible for drug resistance and tumor recurrence. Notch signaling has been shown to promote BCSC survival and self-renewal. Trastuzumab-resistant cells have increased Notch-1 expression. Notch signaling drives cell proliferation in vitro and is required for tumor recurrence in vivo...
May 10, 2018: Oncogene
https://www.readbyqxmd.com/read/29739401/limited-utility-of-tissue-micro-arrays-in-detecting-intra-tumoral-heterogeneity-in-stem-cell-characteristics-and-tumor-progression-markers-in-breast-cancer
#7
Pascale Kündig, Charlotte Giesen, Hartland Jackson, Bernd Bodenmiller, Bärbel Papassotirolopus, Sandra Nicole Freiberger, Catharine Aquino, Lennart Opitz, Zsuzsanna Varga
BACKGROUND: Intra-tumoral heterogeneity has been recently addressed in different types of cancer, including breast cancer. A concept describing the origin of intra-tumoral heterogeneity is the cancer stem-cell hypothesis, proposing the existence of cancer stem cells that can self-renew limitlessly and therefore lead to tumor progression. Clonal evolution in accumulated single cell genomic alterations is a further possible explanation in carcinogenesis. In this study, we addressed the question whether intra-tumoral heterogeneity can be reliably detected in tissue-micro-arrays in breast cancer by comparing expression levels of conventional predictive/prognostic tumor markers, tumor progression markers and stem cell markers between central and peripheral tumor areas...
May 8, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29736694/pre-surgical-trial-of-the-akt-inhibitor-mk-2206-in-patients-with-operable-invasive-breast-cancer-a-new-york-cancer-consortium-trial
#8
K Kalinsky, J A Sparano, X Zhong, E Andreopoulou, B Taback, L Wiechmann, S M Feldman, P Ananthakrishnan, A Ahmad, S Cremers, A N Sireci, J R Cross, D K Marks, P Mundi, E Connolly, K D Crew, M A Maurer, H Hibshoosh, S Lee, D L Hershman
INTRODUCTION: The PI3K/AKT/mTOR pathway is an oncogenic driver in breast cancer (BC). In this multi-center, pre-surgical study, we evaluated the tissue effects of the AKT inhibitor MK-2206 in women with stage I-III BC. MATERIALS AND METHODS: Two doses of weekly oral MK2206 were administered at days - 9 and - 2 before surgery. The primary endpoint was reduction of pAktSer473 in breast tumor tissue from diagnostic biopsy to surgery. Secondary endpoints included changes in PI3K/AKT pathway tumor markers, tumor proliferation (ki-67), insulin growth factor pathway blood markers, pharmacokinetics (PK), genomics, and MK-2206 tolerability...
May 7, 2018: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/29715580/expression-of-p27-and-c-myc-by-immunohistochemistry-in-breast-ductal-cancers-in-african-american-women
#9
Farhan Khan, Luisel J Ricks-Santi, Rabia Zafar, Yasmine Kanaan, Tammey Naab
OBJECTIVES: Proteins p27 and c-Myc are both key players in the cell cycle. While p27, a tumor suppressor, inhibits progression from G1 to S phase, c-Myc, a proto-oncogene, plays a key role in cell cycle regulation and apoptosis. The objective of our study was to determine the association between expression of c-Myc and the loss of p27 by immunohistochemistry (IHC) in the four major subtypes of breast cancer (BC) (Luminal A, Luminal B, HER2, and Triple Negative) and with other clinicopathological factors in a population of 202 African-American (AA) women...
April 5, 2018: Annals of Diagnostic Pathology
https://www.readbyqxmd.com/read/29708077/emerging-drugs-for-the-treatment-of-breast-cancer-brain-metastasis-a-review-of-patent-literature
#10
Maricruz Anaya-Ruiz, Cindy Bandala, Patricia Martinez-Morales, Gerardo Landeta, Rebeca D Martinez-Contreras, Nancy Martinez-Montiel, Martin Perez-Santos
BACKGROUND: Despite dramatic advances in cancer treatment that lead to long-term survival, there is an increasing number of patients presenting with clinical manifestations of cerebral metastasis in breast cancer, for whom only palliative treatment options exist. OBJECTIVE: The present review aims to provide to identify recent patens of breast cancer brain metastasis that may have application in improving cancer treatment. METHOD: Recent patents regarding the breast cancer brain metastasis were obtained from USPTO patent databases, Esp@cenet, Patentscope and Patent Inspiration®...
April 29, 2018: Recent Patents on Anti-cancer Drug Discovery
https://www.readbyqxmd.com/read/29704427/cancer-testis-antigen-plac1-promotes-invasion-and-metastasis-of-breast-cancer-through-furin-nicd-pten-signaling-pathway
#11
Yongfei Li, Jiahui Chu, Jun Li, Wanting Feng, Fan Yang, Yifan Wang, Yanhong Zhang, Chunxiao Sun, Mengzhu Yang, Shauna N Vasilatos, Yi Huang, Ziyi Fu, Yongmei Yin
Plac1 is a cancer-testis antigen that plays a critical role in promoting cancer initiation and progression. However, the clinical significance and mechanism of Plac1 in cancer progression remains elusive. Here we report that Plac1 is an important oncogenic and prognostic factor which physically interacts with Furin to drive breast cancer invasion and metastasis. We have shown that Plac1 expression positively correlates with clinical stage, lymph node metastasis, HR status and overall patient survival. Overexpression of Plac1 promoted invasion and metastasis of breast cancer cells in vitro and in vivo...
April 28, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29700210/genomic-profiling-of-her2-positive-gastric-cancer-pi3k-akt-mtor-pathway-as-predictor-of-outcomes-in-her2-positive-advanced-gastric-cancer-treated-with-trastuzumab
#12
Asunción Díaz-Serrano, Barbara Angulo, Carolina Dominguez, Roberto Pazo-Cid, Antonieta Salud, Paula Jiménez-Fonseca, Ana Leon, Maria Carmen Galan, Maria Alsina, Fernando Rivera, J Carlos Plaza, Luis Paz-Ares, Fernando Lopez-Rios, Carlos Gómez-Martín
BACKGROUND: HER2-positive gastric cancer (GC) affects 7%-34% of patients with GC. Trastuzumab-based first-line treatment has become the standard of care for HER2-positive advanced gastric cancer (AGC). However, there are no clinically validated biomarkers for resistance to HER2-targeted therapies. Upregulation of PI3K pathway and tyrosine kinase receptor (TKR) alterations have been noted as molecular mechanisms of resistance in breast cancer. Our study aimed to perform a molecular characterization of HER2-positive AGC and investigate the role of PI3K/Akt/mTOR signaling pathway activation and TKR gene copy number (GCN) gains as predictive biomarkers in HER2-positive AGC treated with trastuzumab...
April 26, 2018: Oncologist
https://www.readbyqxmd.com/read/29697365/population-based-statistical-inference-for-temporal-sequence-of-somatic-mutations-in-cancer-genomes
#13
Je-Keun Rhee, Tae-Min Kim
BACKGROUND: It is well recognized that accumulation of somatic mutations in cancer genomes plays a role in carcinogenesis; however, the temporal sequence and evolutionary relationship of somatic mutations remain largely unknown. METHODS: In this study, we built a population-based statistical framework to infer the temporal sequence of acquisition of somatic mutations. Using the model, we analyzed the mutation profiles of 1954 tumor specimens across eight tumor types...
April 20, 2018: BMC Medical Genomics
https://www.readbyqxmd.com/read/29695635/mechanisms-of-acquired-resistance-to-trastuzumab-emtansine-in-breast-cancer-cells
#14
Guangmin Li, Jun Guo, Ben-Quan Shen, Daniela Bumbaca Yadav, Mark X Sliwkowski, Lisa M Crocker, Jennifer A Lacap, Gail D Lewis Phillips
The receptor tyrosine kinase HER2 is overexpressed in approximately 20% of breast cancer, and its amplification is associated with reduced survival. Trastuzumab emtansine (Kadcyla®, T-DM1), an antibody-drug conjugate that is comprised of trastuzumab covalently linked to the anti-mitotic agent DM1 through a stable linker, was designed to selectively deliver DM1 to HER2-overexpressing tumor cells. T-DM1 is approved for the treatment of patients with HER2-positive metastatic breast cancer following progression on trastuzumab and a taxane...
April 25, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29693272/baicalein-inhibits-breast-cancer-growth-via-activating-a-novel-isoform-of-the-long-noncoding-rna-pax8-as1-n
#15
Xiaolan Yu, Yong Cao, Li Tang, Yingcheng Yang, Feng Chen, Jiyi Xia
Baicalein, a natural flavonoid, has fascinating anti-cancer properties in breast cancer. Long noncoding RNAs (lncRNAs), a class of transcripts with no protein-coding potential, also exhibit critical roles in breast cancer. However, the molecular mechanisms mediating the anti-cancer properties of baicalein and whether lncRNAs are involved in the anti-cancer effects are still unclear. In this study, we identified a novel isoform of lncRNA PAX8-AS1 (PAX8-AS1-N), which is activated by baicalein in a dose- and time-dependent manner...
April 25, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29684420/novel-cancer-gene-variants-and-gene-fusions-of-triple-negative-breast-cancers-tnbcs-reveal-their-molecular-diversity-conserved-in-the-patient-derived-xenograft-pdx-model
#16
Jaeyun Jung, Kiwon Jang, Jung Min Ju, Eunji Lee, Jong Won Lee, Hee Jung Kim, Jisun Kim, Sae Byul Lee, Beom Seok Ko, Byung Ho Son, Hee Jin Lee, Gyungyup Gong, Sei Yeon Ahn, Jung Kyoon Choi, Shree Ram Singh, Suhwan Chang
Despite the improved 5-year survival rate of breast cancer, triple-negative breast cancer (TNBC) remains a challenge due to lack of effective targeted therapy and higher recurrence and metastasis than other subtypes. To identify novel druggable targets and to understand its unique biology, we tried to implement 24 patient-derived xenografts (PDXs) of TNBC. The overall success rate of PDX implantation was 45%, much higher than estrogen receptor (ER)-positive cases. Immunohistochemical analysis revealed conserved ER/PR/Her2 negativity (with two exceptions) between the original and PDX tumors...
April 20, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29663862/dynamics-and-structural-stability-effects-of-germline-pten-mutations-associated-with-cancer-versus-autism-phenotypes
#17
Iris Nira Smith, Stetson Thacker, Ritika Jaini, Charis Eng
Individuals with germline mutations in the tumor suppressor gene phosphatase and tensin homolog (PTEN), irrespective of clinical presentation, are diagnosed with PTEN hamartoma tumor syndrome (PHTS). PHTS confers a high risk of breast, thyroid, and other cancers or autism spectrum disorder (ASD) with macrocephaly. It remains unclear why mutations in one gene can lead to seemingly disparate phenotypes. Thus, we sought to identify differences in ASD vs. cancer-associated germline PTEN missense mutations by investigating putative structural effects induced by each mutation...
April 17, 2018: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29659014/single-cpg-hypermethylation-allele-methylation-errors-and-decreased-expression-of-multiple-tumor-suppressor-genes-in-normal-body-cells-of-mutation-negative-early-onset-and-high-risk-breast-cancer-patients
#18
Julia Böck, Silke Appenzeller, Larissa Haertle, Tamara Schneider, Andrea Gehrig, Jörg Schröder, Simone Rost, Beat Wolf, Claus R Bartram, Christian Sutter, Thomas Haaf
To evaluate the role of constitutive epigenetic changes in normal body cells of BRCA1/BRCA2-mutation negative patients, we have developed a deep bisulfite sequencing assay targeting the promoter regions of 8 tumor suppressor (TS) genes (BRCA1, BRCA2, RAD51C, ATM, PTEN, TP53, MLH1, RB1) and the estrogene receptor gene (ESR1), which plays a role in tumor progression. We analyzed blood samples of two breast cancer (BC) cohorts with early onset (EO) and high risk (HR) for a heterozygous mutation, respectively, along with age-matched controls...
April 16, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29620260/microrna%C3%A2-142%C3%A2-5p-modulates-breast-cancer-cell-proliferation-and-apoptosis-by-targeting-phosphatase-and-tensin-homolog
#19
Wenda Xu, Weixing Wang
A total of 60 breast cancer (BC) tissues and adjacent healthy tissues from patients who underwent surgery in Renmin Hospital of Wuhan University were collected for analysis in the present study. Results from reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) demonstrated that, compared with the adjacent healthy tissues, the expression levels of microRNA (miR)‑142‑5p were significantly elevated in BC tissues. Bioinformatics analysis was performed using TargetScan for the prediction of potential target sites that matched the seed region of miR‑142‑5p; phosphatase and tensin homolog (PTEN) exhibited the highest score and was selected for further analysis...
March 28, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29617654/identification-of-cdc25-as-a-common-therapeutic-target-for-triple-negative-breast-cancer
#20
Jeff C Liu, Letizia Granieri, Mariusz Shrestha, Dong-Yu Wang, Ioulia Vorobieva, Elizabeth A Rubie, Rob Jones, YoungJun Ju, Giovanna Pellecchia, Zhe Jiang, Carlo A Palmerini, Yaacov Ben-David, Sean E Egan, James R Woodgett, Gary D Bader, Alessandro Datti, Eldad Zacksenhaus
CDK4/6 inhibitors are effective against cancer cells expressing the tumor suppressor RB1, but not RB1-deficient cells, posing the challenge of how to target RB1 loss. In triple-negative breast cancer (TNBC), RB1 and PTEN are frequently inactivated together with TP53. We performed kinome/phosphatase inhibitor screens on primary mouse Rb/p53-, Pten/p53-, and human RB1/PTEN/TP53-deficient TNBC cell lines and identified CDC25 phosphatase as a common target. Pharmacological or genetic inhibition of CDC25 suppressed growth of RB1-deficient TNBC cells that are resistant to combined CDK4/6 plus CDK2 inhibition...
April 3, 2018: Cell Reports
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