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https://www.readbyqxmd.com/read/28223411/pentraxin-3-is-a-pi3k-signaling-target-that-promotes-stem-cell-like-traits-in-basal-like-breast-cancers
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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 6, 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
#8
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
https://www.readbyqxmd.com/read/28153863/the-landscape-of-somatic-genetic-alterations-in-metaplastic-breast-carcinomas
#9
Charlotte K Y Ng, Salvatore Piscuoglio, Felipe C Geyer, Kathleen A Burke, Fresia Pareja, Carey Eberle, Reymond Lim, Rachael Natrajan, Nadeem Riaz, Odette Mariani, Larry Norton, Anne Vincent-Salomon, Y Hannah Wen, Britta Weigelt, Jorge S Reis-Filho
PURPOSE: Metaplastic breast carcinoma (MBC) is a rare and aggressive histologic type of breast cancer predominantly of triple-negative phenotype, and characterized by the presence of malignant cells showing squamous and/or mesenchymal differentiation. We sought to define the repertoire of somatic genetic alterations and the mutational signatures of MBCs. EXPERIMENTAL DESIGN: Whole-exome sequencing was performed in 35 MBCs, with 16, ten and nine classified as harboring chondroid, spindle and squamous metaplasia as the predominant metaplastic component...
February 2, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28152502/methylation-decreases-the-bin1-tumor-suppressor-in-escc-and-restoration-by-decitabine-inhibits-the-epithelial-mesenchymal-transition
#10
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...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28126034/resveratrol-reverses-doxorubicin-resistance-by-inhibiting-epithelial-mesenchymal-transition-emt-through-modulating-pten-akt-signaling-pathway-in-gastric-cancer
#11
Jiahui Xu, Deying Liu, Huilin Niu, Guifang Zhu, Yangwei Xu, Danli Ye, Jian Li, Qingling Zhang
BACKGROUND: Gastric cancer is one of the major causes of cancer-related mortality worldwide. Most of patients presenting with inoperable gastric cancers rely on systemic chemotherapy for prolongation of survival. Doxorubicin (DOX) is one of the important agents against gastric cancer. Acquired DOX-resistance severely impedes the chemotherapeutic effect, invariably leading to poor prognosis. Resveratrol (RES) as a kind of phytoalexin has demonstrated anti-tumor functions in breast cancer and myeloid leukemia, but its function and mechanism are still unknown in gastric cancer treatment...
January 26, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28123607/proteins-involved-in-her2-signalling-pathway-their-relations-and-influence-on-metastasis-free-survival-in-her2-positive-breast-cancer-patients-treated-with-trastuzumab-in-adjuvant-setting
#12
Agnieszka Adamczyk, Aleksandra Grela-Wojewoda, Małgorzata Domagała-Haduch, Aleksandra Ambicka, Agnieszka Harazin-Lechowska, Anna Janecka, Ida Cedrych, Kaja Majchrzyk, Anna Kruczak, Janusz Ryś, Joanna Niemiec
AIM: Resistance to trastuzumab (which is a standard therapy for breast cancer patients with HER2 overexpression) is associated with higher risk of progression or cancer death, and might be related to activation of signalling cascades (PI3K/AKT/mTOR, Ras/Raf/MAPK) and decreased level of their inhibitors. MATERIAL AND METHODS: Formalin-fixed paraffin-embedded tumour specimens from 118 HER2-overexpressing breast cancer patients treated with radical local therapy and trastuzumab in adjuvant setting were used for the assessment of: (1) PIK3CA gene mutations (p...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28116522/molecular-characterization-of-cd44-cd24-ck-cd45-cells-in-benign-and-malignant-breast-lesions
#13
Arnaud Da Cruz Paula, Catarina Leitão, Oriana Marques, Ana Margarida Rosa, Ana Helena Santos, Alexandra Rêma, Maria de Fátima Faria, Ana Rocha, José Luís Costa, Margarida Lima, Carlos Lopes
Breast cancer epithelial cells with the CD44(+)/CD24(-/low) phenotype possess tumor-initiating cells and epithelial-mesenchymal transition (EMT) capacity. Massive parallel sequencing can be an interesting approach to deepen the molecular characterization of these cells. We characterized CD44(+)/CD24(-)/cytokeratin(Ck)(+)/CD45(-) cells isolated through flow cytometry from 43 biopsy and 6 mastectomy samples harboring different benign and malignant breast lesions. The Ion Torrent Ampliseq Cancer Hotspot panel v2 (CHPv2) was used for the identification of somatic mutations in the DNA extracted from isolated CD44(+)/CD24(-)/Ck(+)/CD45(-) cells...
January 23, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28114432/tfdp3-regulates-epithelial-mesenchymal-transition-in-breast-cancer
#14
Kailin Yin, Yanchen Liu, Ming Chu, Yuedan Wang
Breast cancer remains a lethal disease to women due to lymph node metastasis, the tumor microenvironment, secondary resistance and other unknown factors. Several important transcription factors involved in this disease, such as PTEN, p53 and beta-catenin, have been identified and researched in-depth as candidates for targeted therapy in breast cancer. TFDP3 is a new, promising candidate for transcriptional regulation in breast cancer, although it was first identified in hepatocellular carcinoma. Here, we demonstrate that TFDP3 is expressed in a variety of malignancies, normal testis tissue and breast cancer cell lines and thus provide evidence that TFDP3 is a cancer-testis antigen...
2017: PloS One
https://www.readbyqxmd.com/read/28103884/aryl-hydrocarbon-receptor-cytochrome-p450%C3%A2-1a1-pathway-mediates-breast-cancer-stem-cells-expansion-through-pten-inhibition-and-%C3%AE-catenin-and-akt-activation
#15
Abdullah Al-Dhfyan, Ali Alhoshani, Hesham M Korashy
BACKGROUND: Breast cancer stem cells (CSCs) are small sub-type of the whole cancer cells that drive tumor initiation, progression and metastasis. Recent studies have demonstrated a role for the aryl hydrocarbon receptor (AhR)/cytochrome P4501A1 pathway in CSCs expansion. However, the exact molecular mechanisms remain unclear. METHODS: The current study was designed to a) determine the effect of AhR activation and inhibition on breast CSCs development, maintenance, self-renewal, and chemoresistance at the in vitro and in vivo levels and b) explore the role of β-Catenin, PI3K/Akt, and PTEN signaling pathways...
January 19, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28103826/tracking-the-origin-of-simultaneous-endometrial-and-ovarian-cancer-by-next-generation-sequencing-a-case-report
#16
Nadejda Valtcheva, Franziska M Lang, Aurelia Noske, Eleftherios P Samartzis, Anna-Maria Schmidt, Elisa Bellini, Daniel Fink, Holger Moch, Markus Rechsteiner, Konstantin J Dedes, Peter J Wild
BACKGROUND: Endometrioid adenocarcinoma of the uterus and ovarian endometrioid carcinoma share many morphological and molecular features. Differentiation between simultaneous primary carcinomas and ovarian metastases of an endometrial cancer may be very challenging but is essential for prognostic and therapeutic considerations. CASE PRESENTATION: In the present case study of a 33 year-old patient we used targeted amplicon next-generation re-sequencing for clarifying the origin of synchronous endometrioid cancer of the corpus uteri and the left ovary...
January 19, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28075472/suppression-of-pten-akt-signaling-decreases-the-expression-of-tubb3-and-top2a-with-subsequent-inhibition-of-cell-growth-and-induction-of-apoptosis-in-human-breast-cancer-mcf-7-cells-via-atp-and-caspase-3-signaling-pathways
#17
Zhenhua Yang, Ying Liu, Changzheng Shi, Yuqin Zhang, Rongzhao Lv, Rong Zhang, Qian Wang, Yiming Wang
The aim of the present study was to evaluate the effects of PTEN/AKT signaling on TUBB3 and TOP2A expression and on the subsequent cell growth of human breast cancer MCF-7 cells. We found that the disease-free survival (DFS) and overall survival (OS) of breast cancer patients with TUBB3‑positive tumors were lower than these rates in the patients with TUBB3-negative tumors. Meanwhile, DFS and OS of breast cancer patients with TOP2A-positive tumors were also lower than these rates in patients with TOP2A-negative tumors...
February 2017: Oncology Reports
https://www.readbyqxmd.com/read/28074344/multiple-oral-mucosal-hamartomas-in-a-34-year-old-female
#18
Jeffrey A Elo, Ho-Hyun Sun, Joel M Laudenbach, Hardev M Singh
A case of Cowden syndrome (CS) is described in a 34-year-old African American female who reported a history of breast and thyroid malignancies. Clinical examination demonstrated multiple soft, white-pink papules across multiple mucosal surfaces of the oral cavity. Microscopy of the lesions revealed hyperkeratotic surface squamous epithelium with papillomatosis and acanthosis along with elongated rete processes. A genomic polymerase chain reaction direct sequencing using the patient's blood was positive for mutations of the PTEN gene typical of CS...
January 10, 2017: Head and Neck Pathology
https://www.readbyqxmd.com/read/28049216/cancer-implications-for-patients-with-endometriosis
#19
Mary Ann Wilbur, Ie-Ming Shih, James H Segars, Amanda N Fader
Endometriosis is defined as the presence of viable endometrial glands and stroma outside of the uterus. It is a common disease, occurring in 5 to 15% of all women. Endometriosis is associated with chronic pelvic pain and infertility and often requires surgical intervention for definitive treatment. Although it is a benign gynecologic condition, endometriosis shares pathophysiologic features with cancer. In recent years, both histologic and epidemiologic evidence has accumulated, suggesting that ovarian endometriosis may give rise to malignant ovarian tumors, primarily those that are epithelial in origin, known as endometriosis-associated ovarian carcinoma (EAOC) including ovarian clear cell carcinoma, endometrioid carcinoma, and the least common, seromucinous tumors...
January 2017: Seminars in Reproductive Medicine
https://www.readbyqxmd.com/read/28034453/dna-damage-repair-in-breast-cancer-and-its-therapeutic-implications
#20
REVIEW
Reem Ali, Emad A Rakha, Srinivasan Madhusudan, Helen E Bryant
The DNA damage response (DDR) involves the activation of numerous cellular activities that repair DNA lesions and maintain genomic integrity, and is critical in preventing tumorigenesis. Inherited or acquired mutations in specific genes involved in the DNA damage response, for example the breast cancer susceptibility genes 1/2 (BRCA1/2), phosphatase and tensin homolog (PTEN) and P53 are associated with various subtypes of breast cancer. Such changes can render breast cancer cells particularly sensitive to specific DNA damage response inhibitors, for example BRCA1/2 germline mutated cells are sensitive to poly (ADP-ribose) polymerase (PARP) inhibitors...
February 2017: Pathology
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