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https://www.readbyqxmd.com/read/28329541/cowden-syndrome-presenting-with-trichilemmomas
#1
Elise Ng, Vitaly Terushkin, Shane A Meehan, Roger Ho, Miriam Keltz Pomeranz
Cowden syndrome (CS) is a genetic cancerpredisposition syndrome that is associated withgermline mutations in the phosphate and tensinhomologue deleted on chromosome ten (PTEN)tumor suppressor gene. It is characterizedby the formation of benign and malignanttumors. Characteristic benign tumors includetrichilemmommas, acral keratoses, mucocutaneousneuromas, and oral papillomas. The most commonmalignant condition include breast, thyroid, andendometrial cancers. We present a case of a30-year-old woman with CS, who initially presentedwith trichilemmomas that were misdiagnosed ascomedonal acne...
December 15, 2016: Dermatology Online Journal
https://www.readbyqxmd.com/read/28321778/effects-of-mir-21-downregulation-and-silibinin-treatment-in-breast-cancer-cell-lines
#2
Zohreh Jahanafrooz, Nasrin Motamed, Behnaz Bakhshandeh
Silibinin is a natural polyphenol with high antioxidant and anticancer properties, which causes cell cycle arrest and apoptosis in most cancer cell types including breast cancer, but the in-line mechanisms, are still unknown. Silibinin significantly downregulated oncomiR miR-21 expression in breast cancer cells. Here the effect of anti-miR-21 on cell viability, apoptotic induction, cell cycle distribution, and the expression levels of downstream targets of miR-21 were investigated in MCF-7 and T47D cells. MiR-21 mimic transfection was also applied in silibinin treated samples to evaluate functional role of miR-21downregulation on silibinin effects...
March 20, 2017: Cytotechnology
https://www.readbyqxmd.com/read/28319090/a-single-copy-sleeping-beauty-transposon-mutagenesis-screen-identifies-new-pten-cooperating-tumor-suppressor-genes
#3
Jorge de la Rosa, Julia Weber, Mathias Josef Friedrich, Yilong Li, Lena Rad, Hannes Ponstingl, Qi Liang, Sandra Bernaldo de Quirós, Imran Noorani, Emmanouil Metzakopian, Alexander Strong, Meng Amy Li, Aurora Astudillo, María Teresa Fernández-García, María Soledad Fernández-García, Gary J Hoffman, Rocío Fuente, George S Vassiliou, Roland Rad, Carlos López-Otín, Allan Bradley, Juan Cadiñanos
The overwhelming number of genetic alterations identified through cancer genome sequencing requires complementary approaches to interpret their significance and interactions. Here we developed a novel whole-body insertional mutagenesis screen in mice, which was designed for the discovery of Pten-cooperating tumor suppressors. Toward this aim, we coupled mobilization of a single-copy inactivating Sleeping Beauty transposon to Pten disruption within the same genome. The analysis of 278 transposition-induced prostate, breast and skin tumors detected tissue-specific and shared data sets of known and candidate genes involved in cancer...
March 20, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28301567/integrated-analysis-of-promoter-mutation-methylation-and-expression-of-akt1-gene-in-chinese-breast-cancer-patients
#4
Jianfu Heng, Xinwu Guo, Wenhan Wu, Yue Wang, Guoli Li, Ming Chen, Limin Peng, Shouman Wang, Lizhong Dai, Lili Tang, Jun Wang
BACKGROUND: As downstream mediators of PI3K /PTEN /AKT /mTORC1 pathway, the AKT isoforms play critical roles in tumorgenesis. Although the pleiotropic effects of AKT1 in breast cancer have been reported, the genetic and epigenetic characteristics of AKT1 promoter region in breast cancer remains to be identified. In this study we aimed to investigate the promoter mutation spectrum, methylation and gene expression pattern of AKT1 and their relationship with breast cancer. METHODS: By using PCR target sequence enrichment and next-generation sequencing technology, we sequenced AKT1 promoter region in pairs of breast tumor and normal tissues from 95 unselected Chinese breast cancer patients...
2017: PloS One
https://www.readbyqxmd.com/read/28283772/identification-genetic-testing-and-management-of-hereditary-melanoma
#5
Sancy A Leachman, Olivia M Lucero, Jone E Sampson, Pamela Cassidy, William Bruno, Paola Queirolo, Paola Ghiorzo
Several distinct melanoma syndromes have been defined, and genetic tests are available for the associated causative genes. Guidelines for melanoma genetic testing have been published as an informal "rule of twos and threes," but these guidelines apply to CDKN2A testing and are not intended for the more recently described non-CDKN2A melanoma syndromes. In order to develop an approach for the full spectrum of hereditary melanoma patients, we have separated melanoma syndromes into two types: "melanoma dominant" and "melanoma subordinate...
March 10, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28272775/cryptotanshinone-inhibition-of-mammalian-target-of-rapamycin-pathway-is-dependent-on-oestrogen-receptor-alpha-in-breast-cancer
#6
Yanhong Pan, Junfeng Shi, Wenting Ni, Yuping Liu, Siliang Wang, Xu Wang, Zhonghong Wei, Aiyun Wang, Wenxing Chen, Yin Lu
Cryptotanshinone (CPT) has been demonstrated to inhibit proliferation and mammalian target of rapamycin (mTOR) pathway in MCF-7 breast cancer cells. However, the same results are unable to be repeated in MDA-MB-231 cells. Given the main difference of oestrogen receptor α (ERα) between two types of breast cancer cells, It is possibly suggested that CPT inhibits mTOR pathway dependent on ERα in breast cancer. CPT could significantly inhibit cell proliferation of ERα-positive cancer cells, whereas ERα-negative cancer cells are insensitive to CPT...
March 8, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28258440/comprehensive-characterization-of-genes-associated-with-the-tp53-signal-transduction-pathway-in-various-tumors
#7
Shumpei Ohnami, Keiichi Ohshima, Takeshi Nagashima, Kenichi Urakami, Yuji Shimoda, Junko Saito, Akane Naruoka, Keiichi Hatakeyama, Tohru Mochizuki, Masakuni Serizawa, Sumiko Ohnami, Masatoshi Kusuhara, Ken Yamaguchi
The TP53 signal transduction pathway is an attractive target for cancer treatments. In this study, we conducted a comprehensive molecular evaluation of 907 patients with cancer in Japan to identify genomic alterations in the TP53 pathway. TP53 mutations were frequently detected in many cancers, except melanoma, thymic tumors, gastrointestinal stromal tumors, and renal cancers. The frequencies of non-synonymous single nucleotide variants (SNVs) in the TP53 family members TP63 and TP73 were relatively low, although genes with increased frequencies of SNVs were as follows: PTEN (11...
March 3, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28253285/pten-expression-as-a-predictor-for-the-response-to-trastuzumab-based-therapy-in-her-2-overexpressing-metastatic-breast-cancer
#8
Daphne Gschwantler-Kaulich, Yen Y Tan, Eva-Maria Fuchs, Gernot Hudelist, Wolfgang J Köstler, Angelika Reiner, Carmen Leser, Mohamed Salama, Johannes Attems, Christine Deutschmann, Christoph C Zielinski, Christian F Singer
BACKGROUND: Even though trastuzumab is an effective therapy in early stage Her-2+ breast cancer, 40-50% of advanced Her-2+ breast cancer patients develop trastuzumab resistance. A potential resistance mechanism is aberrant downstream signal transmission due to loss of phosphatase and tensin homologue (PTEN). This study investigated the relationship between the expression of PTEN and trastuzumab response in Her-2 overexpressing metastatic breast cancer patients. METHODS: Between 2000 and 2007, 164 patients with Her-2+ metastatic breast cancer received trastuzumab-based therapy in our institution...
2017: PloS One
https://www.readbyqxmd.com/read/28251929/transposon-insertional-mutagenesis-in-mice-identifies-human-breast-cancer-susceptibility-genes-and-signatures-for-stratification
#9
Liming Chen, Piroon Jenjaroenpun, Andrea Mun Ching Pillai, Anna V Ivshina, Ghim Siong Ow, Motakis Efthimios, Tang Zhiqun, Tuan Zea Tan, Song-Choon Lee, Keith Rogers, Jerrold M Ward, Seiichi Mori, David J Adams, Nancy A Jenkins, Neal G Copeland, Kenneth Hon-Kim Ban, Vladimir A Kuznetsov, Jean Paul Thiery
Robust prognostic gene signatures and therapeutic targets are difficult to derive from expression profiling because of the significant heterogeneity within breast cancer (BC) subtypes. Here, we performed forward genetic screening in mice using Sleeping Beauty transposon mutagenesis to identify candidate BC driver genes in an unbiased manner, using a stabilized N-terminal truncated β-catenin gene as a sensitizer. We identified 134 mouse susceptibility genes from 129 common insertion sites within 34 mammary tumors...
March 1, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28249898/defining-cancer-subpopulations-by-adaptive-strategies-rather-than-molecular-properties-provides-novel-insights-into-intratumoral-evolution
#10
Arig Ibrahim-Hashim, Mark Robertson-Tessi, Pedro Enrizues-Navas, Mehdi Damaghi, Yoganand Balagurunathan, Jonathan W Wojtkowiak, Shonagh Russell, Kam Yoonseok, Mark C Lloyd, Marilyn M Bui, Joel S Brown, Alexander Ra Anderson, Robert J Gillies, Robert A Gatenby
Ongoing intratumoral evolution is apparent in molecular variations among cancer cells from different regions of the same tumor, but genetic data alone provide little insight into environmental selection forces and cellular phenotypic adaptations that govern the underlying Darwinian dynamics. In three spontaneous murine cancers (prostate cancers in TRAMP and PTEN mice, pancreatic cancer in KPC mice), we identified two subpopulations with distinct niche-construction adaptive strategies that remained stable in culture: (1) Invasive cells that produce an acidic environment via upregulated aerobic glycolysis, and (2) Non-invasive cells that were angiogenic and metabolically near-normal...
March 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28247964/pi-3-4-p2-plays-critical-roles-in-the-regulation-of-focal-adhesion-dynamics-of-mda-mb-231-breast-cancer-cells
#11
Miki Fukumoto, Takeshi Ijuin, Tadaomi Takenawa
Phosphoinositides play pivotal roles in the regulation of cancer cell phenotypes. Among them, phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2 ) localizes to the invadopodia, and positively regulates tumor cell invasion. In this study, we examined the effect of PI(3,4)P2 on focal adhesion dynamics in MDA-MB-231 basal breast cancer cells. Knockdown of SHIP2, a phosphatidylinositol 3,4,5-trisphosphatase (PIP3 ) 5-phosphatase that generates PI(3,4)P2 , in MDA-MB-231 breast cancer cells, induced the development of focal adhesions and cell spreading, leading to the suppression of invasion...
March 1, 2017: Cancer Science
https://www.readbyqxmd.com/read/28236692/synthesis-and-characterization-of-folate-decorated-albumin-bio-conjugate-nanoparticles-loaded-with-a-synthetic-curcumin-difluorinated-analogue
#12
Kaustubh A Gawde, Prashant Kesharwani, Samaresh Sau, Fazlul H Sarkar, Subhash Padhye, Sushil K Kashaw, Arun K Iyer
Albumin-bound paclitaxel colloidal nanoparticle (Abraxane®) is an FDA approved anticancer formulation available in the market. It is a suspension which is currently used therapeutically for treating cancers of the breast, lung, and pancreas among others. CDF is a novel new and potent synthetic curcumin analogue that is widely used for breast and ovarian cancer. The aim of this study was to use biocompatible albumin as well as folate decorated albumin to formulate colloidal nanoparticles encapsulating curcumin difluorinated (CDF)...
February 14, 2017: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/28223411/pentraxin-3-is-a-pi3k-signaling-target-that-promotes-stem-cell-like-traits-in-basal-like-breast-cancers
#13
Clémence Thomas, Whitney Henry, Benjamin G Cuiffo, Anthony Y Collmann, Elisabetta Marangoni, Vanessa Benhamo, Manoj K Bhasin, Cheng Fan, Laetitia Fuhrmann, Albert S Baldwin, Charles Perou, Anne Vincent-Salomon, Alex Toker, Antoine E Karnoub
Basal-like breast cancers (BLBCs) exhibit hyperactivation of the phosphoinositide 3-kinase (PI3K) signaling pathway because of the frequent mutational activation of the PIK3CA catalytic subunit and the genetic loss of its negative regulators PTEN (phosphatase and tensin homolog) and INPP4B (inositol polyphosphate-4-phosphatase type II). However, PI3K inhibitors have had limited clinical efficacy in BLBC management because of compensatory amplification of PI3K downstream signaling loops. Therefore, identification of critical PI3K mediators is paramount to the development of effective BLBC therapeutics...
February 21, 2017: Science Signaling
https://www.readbyqxmd.com/read/28213783/high-pten-gene-expression-is-a-negative-prognostic-marker-in-human-primary-breast-cancers-with-preserved-p53-function
#14
Synnøve Yndestad, Eilin Austreid, Stian Knappskog, Ranjan Chrisanthar, Peer Kåre Lilleng, Per Eystein Lønning, Hans Petter Eikesdal
PURPOSE: PTEN is an important tumor suppressor in breast cancer. Here, we examined the prognostic and predictive value of PTEN and PTEN pseudogene (PTENP1) gene expression in patients with locally advanced breast cancer given neoadjuvant chemotherapy. METHODS: The association between pretreatment PTEN and PTENP1 gene expression, response to neoadjuvant chemotherapy, and recurrence-free and disease-specific survival was assessed in 364 patients with locally advanced breast cancer given doxorubicin, 5-fluorouracil/mitomycin, or epirubicin versus paclitaxel in three phase II prospective studies...
February 17, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28196852/inpp4b-and-pten-loss-leads-to-pi-3-4-p2-accumulation-and-inhibition-of-pi3k-in-tnbc
#15
Darien E Reed, Kevan M Shokat
Triple-negative breast cancer [TNBC, lacks expression of estrogen receptor (ER), progesterone receptor (PR) and amplification of HER2/Neu] remains one of the most aggressive subtypes, affects the youngest patients and still lacks an effective targeted therapy(1,2). Both phosphatidylinositol-3-kinase (PI3K)-α and -β contribute to oncogenesis of solid tumors, including the development of breast cancer(3). Inositol polyphosphate-4-phosphatase type II (INPP4B) catalyzes the removal of the 4'-phosphate of phosphatidylinositol-(3,4-bisphosphate (PI-3,4-P2) creating phosphatidylinositol-3-phosphate(4)...
February 14, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28191283/active-%C3%AE-catenin-is-regulated-by-the-pten-pi3-kinase-pathway-a-role-for-protein-phosphatase-pp2a
#16
Amit Persad, Geetha Venkateswaran, Li Hao, Maria E Garcia, Jenny Yoon, Jaskiran Sidhu, Sujata Persad
Dysregulation of Wnt/β-catenin signaling has been associated with the development and progression of many cancers. The stability and subcellular localization of β-catenin, a dual functional protein that plays a role in intracellular adhesion and in regulating gene expression, is tightly regulated. However, little is known about the transcriptionally active form of β-catenin, Active Beta Catenin (ABC), that is unphosphorylated at serine 37 (Ser37) and threonine 41 (Thr41). Elucidating the mechanism by which β-catenin is activated to generate ABC is vital to the development of therapeutic strategies to block β-catenin signaling for cancer treatment...
November 2016: Genes & Cancer
https://www.readbyqxmd.com/read/28187748/characterization-of-ovarian-clear-cell-carcinoma-using-target-drug-based-molecular-biomarkers-implications-for-personalized-cancer-therapy
#17
Mengjiao Li, Haoran Li, Fei Liu, Rui Bi, Xiaoyu Tu, Lihua Chen, Shuang Ye, Xi Cheng
BACKGROUND: It has long been appreciated that different subtypes (serous, clear cell, endometrioid and mucinous) of epithelial ovarian carcinoma (EOC) have distinct pathogenetic pathways. However, clinical management, especially chemotherapeutic regimens, for EOC patients is not subtype specific. Ovarian clear cell carcinoma (CCC) is a rare histological subtype of EOC, which exhibits high rates of recurrence and low chemosensitivity. We assessed potential therapeutic targets for ovarian CCC patients through analyzing the variation of drug-based molecular biomarkers expression between ovarian CCC and high-grade serous carcinoma (HGSC)...
February 10, 2017: Journal of Ovarian Research
https://www.readbyqxmd.com/read/28183251/the-real-impact-of-target-therapy-in-breast-cancer-patients-between-hope-and-reality
#18
Sebastiano Bordonaro, Massimiliano Berretta, Antonino Carmelo Tralongo, Silvia Clementi, Brigida Stanzione, Paolo Tralongo
Over the last 15 years, we have seen a huge expansion of the development of drugs directed against biomolecular targets within breast cancer cells. The over-expression of certain receptors (ER, PgR, HER-2, VEGF-R), as well as alteration of several intracellular signal transduction pathways (the PI3K-AKT-mTOR pathway, MEK-MAPK pathway, loss of PTEN, etc ...) have a great impact on the likelihood of recurrence and progression of the disease, influencing the natural history of breast cancer. The recent biomolecular classification of breast cancer (Luminal A / B, HER2-driven, Basal Like) allowed finally to identify specific treatments against molecular target to associate or not to traditional chemotherapy, and to use in relation to the prognosis of the disease...
February 8, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28166537/synthetic-essentiality-of-chromatin-remodelling-factor-chd1-in-pten-deficient-cancer
#19
Di Zhao, Xin Lu, Guocan Wang, Zhengdao Lan, Wenting Liao, Jun Li, Xin Liang, Jasper Robin Chen, Sagar Shah, Xiaoying Shang, Ming Tang, Pingna Deng, Prasenjit Dey, Deepavali Chakravarti, Peiwen Chen, Denise J Spring, Nora M Navone, Patricia Troncoso, Jianhua Zhang, Y Alan Wang, Ronald A DePinho
Synthetic lethality and collateral lethality are two well-validated conceptual strategies for identifying therapeutic targets in cancers with tumour-suppressor gene deletions. Here, we explore an approach to identify potential synthetic-lethal interactions by screening mutually exclusive deletion patterns in cancer genomes. We sought to identify 'synthetic-essential' genes: those that are occasionally deleted in some cancers but are almost always retained in the context of a specific tumour-suppressor deficiency...
February 23, 2017: Nature
https://www.readbyqxmd.com/read/28165066/microrna-130b-targets-pten-to-mediate-drug-resistance-and-proliferation-of-breast-cancer-cells-via-the-pi3k-akt-signaling-pathway
#20
Yuan Miao, Wei Zheng, Nana Li, Zhen Su, Lifen Zhao, Huimin Zhou, Li Jia
Multidrug resistance (MDR) correlates with treatment failure and poor prognosis among breast cancer patients. This study was aimed to investigate the possible mechanism by which microRNA-130b-3p (miR-130b) mediates the chemoresistance and proliferation of breast cancer. MiR-130b was found to be up-regulated in tumor tissues versus adjacent tissues of breast cancer, as well as in adriamycin (ADR) resistant breast cancer cell line (MCF-7/ADR) versus its parental line (MCF-7) and the non-malignant breast epithelial cell line (MCF-10A), demonstrating its crucial relevance for breast cancer biology...
February 6, 2017: Scientific Reports
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