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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
#1
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
#2
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
#3
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
#4
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
#5
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 3, 2017: Seminars in Reproductive Medicine
https://www.readbyqxmd.com/read/28034453/dna-damage-repair-in-breast-cancer-and-its-therapeutic-implications
#6
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...
December 26, 2016: Pathology
https://www.readbyqxmd.com/read/28027327/mutational-profile-of-metastatic-breast-cancers-a-retrospective-analysis
#7
Celine Lefebvre, Thomas Bachelot, Thomas Filleron, Marion Pedrero, Mario Campone, Jean-Charles Soria, Christophe Massard, Christelle Lévy, Monica Arnedos, Magali Lacroix-Triki, Julie Garrabey, Yannick Boursin, Marc Deloger, Yu Fu, Frédéric Commo, Véronique Scott, Ludovic Lacroix, Maria Vittoria Dieci, Maud Kamal, Véronique Diéras, Anthony Gonçalves, Jean-Marc Ferrerro, Gilles Romieu, Laurence Vanlemmens, Marie-Ange Mouret Reynier, Jean-Christophe Théry, Fanny Le Du, Séverine Guiu, Florence Dalenc, Gilles Clapisson, Hervé Bonnefoi, Marta Jimenez, Christophe Le Tourneau, Fabrice André
BACKGROUND: Major advances have been achieved in the characterization of early breast cancer (eBC) genomic profiles. Metastatic breast cancer (mBC) is associated with poor outcomes, yet limited information is available on the genomic profile of this disease. This study aims to decipher mutational profiles of mBC using next-generation sequencing. METHODS AND FINDINGS: Whole-exome sequencing was performed on 216 tumor-blood pairs from mBC patients who underwent a biopsy in the context of the SAFIR01, SAFIR02, SHIVA, or Molecular Screening for Cancer Treatment Optimization (MOSCATO) prospective trials...
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/28011157/increased-identification-of-candidates-for-high-risk-breast-cancer-screening-through-expanded-genetic-testing
#8
Eric T Rosenthal, Brent Evans, John Kidd, Krystal Brown, Heidi Gorringe, Michael van Orman, Susan Manley
PURPOSE: Breast MRI screening is recommended for women with a >20% lifetime risk for breast cancer on the basis of estimates derived from risk models dependent largely on family history. Alternatively, a >20% lifetime risk can be established through genetic testing of BRCA1 and BRCA2, as well as a growing selection of other genes associated with inherited breast cancer risk. The aim of this study was to quantify the impact of testing for genes other than BRCA1/2 and the extent to which mutation carriers in these genes would have been identified as candidates for enhanced screening on the basis of family history alone...
December 20, 2016: Journal of the American College of Radiology: JACR
https://www.readbyqxmd.com/read/28008153/pten-mediates-the-cross-talk-between-breast-and-glial-cells-in-brain-metastases-leading-to-rapid-disease-progression
#9
Ina Hohensee, Han-Ning Chuang, Astrid Grottke, Stefan Werner, Alexander Schulte, Stefan Horn, Katrin Lamszus, Kai Bartkowiak, Isabell Witzel, Manfred Westphal, Jakob Matschke, Markus Glatzel, Manfred Jücker, Tobias Pukrop, Klaus Pantel, Harriet Wikman
Despite improvement of therapeutic treatments for breast cancer, the development of brain metastases has become a major limitation to life expectancy for many patients. Brain metastases show very commonly alterations in EGFR and HER2 driven pathways, of which PTEN is an important regulator. Here, we analyzed PTEN expression in 111 tissue samples of breast cancer brain metastases (BCBM). Loss of PTEN was found in a substantial proportion of BCBM samples (48.6%) and was significantly associated with triple-negative breast cancer (67...
December 20, 2016: Oncotarget
https://www.readbyqxmd.com/read/27994679/brown-seaweed-fucoidan-inhibits-cancer-progression-by-dual-regulation-of-mir-29c-adam12-and-mir-17-5p-pten-axes-in-human-breast-cancer-cells
#10
Szu-Yuan Wu, Alexander T H Wu, Kevin Sheng-Po Yuan, Shing Hwa Liu
In this study, we observed that brown seaweed fucoidan inhibited human breast cancer progression by upregulating microRNA (miR)-29c and downregulating miR-17-5p, thereby suppressing their target genes, a disintegrin and metalloproteinase 12 (ADAM12) and phosphatase and tensin homolog (PTEN), respectively. Moreover, fucoidan reduced the luciferase activity of 3'-untranslated region reporter; treatment of cells with the miR-29c mimic or miR-17-5p inhibitor also produced similar results. These effects of fucoidan inhibited the epithelial-mesenchymal transition in breast cancer cells, as evidenced by an increase in E-cadherin and a drop in N-cadherin, and inhibited breast cancer cell survival, as evidenced by the activation of the phosphoinositide 3-kinase/Akt pathway...
2016: Journal of Cancer
https://www.readbyqxmd.com/read/27983521/expression-of-ttf-1-in-breast-cancer-independently-of-er-expression-a-case-report-and-pathogenic-implications
#11
Ioannis A Voutsadakis, Paul Mozarowski
Thyroid Transcription Factor 1 (TTF-1) is often used for the immunohistochemical evaluation of lung cancers, as a significant proportion of these cancers are positive while other adenocarcinomas are usually negative. Breast cancers are known to express TTF-1 only in a small minority of cases but this may be problematic when this staining is used for its differential diagnosis from lung cancer. We present a case of ER-positive breast cancer in 30% of tumor cells that was also TTF-1 positive in some areas of the primary tumor but lost ER expression completely in the metastatic recurrence site while retaining TTF-1 positivity...
December 14, 2016: Breast Disease
https://www.readbyqxmd.com/read/27912236/prognostic-role-of-pten-gene-expression-in-breast-cancer-patients-from-north-east-iran
#12
Rahim Golmohammadi, Mohammad Hassan Rakhshani, Ali Reza Moslem, Akbar Pejhan
Background: PTEN protein is one of the most important tumour suppressor factors which is detectable by immunohistochemistry. The goal of the present study was to investigate the prognostic role of PTEN gene expression in breast cancer patients. Materials and Methods: This descriptive-analytical study was conducted on 100 breast cancer patients referred to Sabzevar hospitals in the north-east of Iran between 2010 and 2011, who were followed up to 2015. PTEN gene expression in tissue samples was determined using specific monoclonal antibodies and data were analyzed using Chi-square test and Fisher’s exact test...
January 9, 2016: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/27903677/combined-inhibition-of-both-p110%C3%AE-and-p110%C3%AE-isoforms-of-phosphatidylinositol-3-kinase-is-required-for-sustained-therapeutic-effect-in-pten-deficient-er-breast-cancer
#13
Sarah R Hosford, Lloye M Dillon, Stephanie J Bouley, Rachele Rosati, Wei Yang, Vivian S Chen, Eugene Demidenko, Rocco P Morra, Todd W Miller
PURPOSE: Determine the roles of the phosphatidylinositol 3-kinase (PI3K) isoforms p110α and p110β in PTEN-deficient, estrogen receptor α (ER)-positive breast cancer, and the therapeutic potential of isoform-selective inhibitors. EXPERIMENTAL DESIGN: Anti-estrogen-sensitive and -resistant PTEN-deficient, ER+ human breast cancer cell lines, and mice bearing anti-estrogen-resistant xenografts were treated with the anti-estrogen fulvestrant, the p110α inhibitor BYL719, the p110β inhibitor GSK2636771, or combinations...
November 30, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27899992/beside-p53-and-pten-identification-of-molecular-alterations-of-the-ras-mapk-and-pi3k-akt-signaling-pathways-in-high-grade-serous-ovarian-carcinomas-to-determine-potential-novel-therapeutic-targets
#14
Shuhui Chen, Elisa Cavazza, Catherine Barlier, Julia Salleron, Pierre Filhine-Tresarrieu, Céline Gavoilles, Jean-Louis Merlin, Alexandre Harlé
Despite great histological and molecular heterogeneity, the clinical management of high-grade ovarian carcinomas remains unspecialized. As a major subgroup, high-grade serous ovarian carcinomas (HGSOCs) require novel therapies. In addition to utilizing conventional histological prognostic markers and performing oncogenetic investigations, the molecular diagnostic method of next generation sequencing (NGS) was performed to identify 'druggable' targets that could provide access to innovative therapy. The present study was performed in 45 HGSOC patients (mean age, 59...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27864890/anti-egfr-monoclonal-antibodies-enhance-sensitivity-to-dna-damaging-agents-in-brca1-mutated-and-pten-wild-type-triple-negative-breast-cancer-cells
#15
Abderrahim El Guerrab, Mahchid Bamdad, Yves-Jean Bignon, Frédérique Penault-Llorca, Corinne Aubel
Increased epidermal growth factor receptor (EGFR) expression in triple-negative breast cancer (TNBC) is recognized as a promising therapeutic target, specifically through the use of selective EGFR inhibitors combined with chemotherapies. TNBC is characterized by genetic instability that leads to increased sensitivity to cytotoxic agents. We analyzed the effect of anti-EGFR monoclonal antibodies (mAbs; cetuximab and panitumumab) in combination with chemotherapeutic agents (docetaxel, cisplatin and epirubicin) on EGFR-expressing TNBC cell lines that have different mutation statuses for one oncogene (KRAS) and two tumor suppressor genes (PTEN and BRCA1)...
November 19, 2016: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27864123/pten-pi3k-akt-protein-expression-is-related-to-clinicopathologic-features-and-prognosis-in-breast-cancer-with-axillary-lymph-node-metastases
#16
Ling-Li Wang, Shuai Hao, Shu Zhang, Ling-Ji Guo, Chun-Yan Hu, Gang Zhang, Bo Gao, Jian-Jie Zhao, Yan Jiang, Wu-Guo Tian, Jun Wang, Dong-Lin Luo
We explored the relations between PTEN/PI3K/AKT expression and clinicopathologic characteristics and prognosis in breast cancer patients with and without axillary lymph node metastasis (LNM). Tissues and follow-up data from 142 patients with (LNM group) and 154 without (non-LNM group) metastases were collected. Expression of PTEN/PI3K/AKT was detected using immunohistochemistry staining. With axillary LNM, the positive rate of PTEN was reduced, whereas that of PI3K and AKT was increased. Expression of AKT was negatively correlated with PTEN expression but positively correlated with PI3K expression...
November 15, 2016: Human Pathology
https://www.readbyqxmd.com/read/27849608/transposon-mutagenesis-identifies-genes-that-cooperate-with-mutant-pten-in-breast-cancer-progression
#17
Roberto Rangel, Song-Choon Lee, Kenneth Hon-Kim Ban, Liliana Guzman-Rojas, Michael B Mann, Justin Y Newberg, Takahiro Kodama, Leslie A McNoe, Luxmanan Selvanesan, Jerrold M Ward, Alistair G Rust, Kuan-Yew Chin, Michael A Black, Nancy A Jenkins, Neal G Copeland
Triple-negative breast cancer (TNBC) has the worst prognosis of any breast cancer subtype. To better understand the genetic forces driving TNBC, we performed a transposon mutagenesis screen in a phosphatase and tensin homolog (Pten) mutant mice and identified 12 candidate trunk drivers and a much larger number of progression genes. Validation studies identified eight TNBC tumor suppressor genes, including the GATA-like transcriptional repressor TRPS1 Down-regulation of TRPS1 in TNBC cells promoted epithelial-to-mesenchymal transition (EMT) by deregulating multiple EMT pathway genes, in addition to increasing the expression of SERPINE1 and SERPINB2 and the subsequent migration, invasion, and metastasis of tumor cells...
November 29, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27846853/dgca-a-comprehensive-r-package-for-differential-gene-correlation-analysis
#18
Andrew T McKenzie, Igor Katsyv, Won-Min Song, Minghui Wang, Bin Zhang
BACKGROUND: Dissecting the regulatory relationships between genes is a critical step towards building accurate predictive models of biological systems. A powerful approach towards this end is to systematically study the differences in correlation between gene pairs in more than one distinct condition. RESULTS: In this study we develop an R package, DGCA (for Differential Gene Correlation Analysis), which offers a suite of tools for computing and analyzing differential correlations between gene pairs across multiple conditions...
November 15, 2016: BMC Systems Biology
https://www.readbyqxmd.com/read/27811364/erbb2-mutation-is-associated-with-a-worse-prognosis-in-patients-with-cdh1-altered-invasive-lobular-cancer-of-the-breast
#19
Zheng Ping, Gene P Siegal, Shuko Harada, Isam-Eldin Eltoum, Mariam Youssef, Tiansheng Shen, Jianbo He, Yingjie Huang, Dongquan Chen, Yiping Li, Kirby I Bland, Helena R Chang, Dejun Shen
E-cadherin (CDH1) is a glycoprotein that mediates adhesion between epithelial cells and also suppresses cancer invasion. Mutation or deletion of the CDH1 gene has been reported in 30-60% cases of invasive lobular carcinoma (ILC). However, little is known about genomic differences between ILC with and without a CDH1 alteration. Therefore, we analyzed whole genome sequencing data of 169 ILC cases from The Cancer Genome Atlas (TCGA) to address this deficiency. Our study shows that CDH1 gene was altered in 59.2% (100/169) of ILC...
November 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27808478/lacrimal-gland-ductal-carcinomas-clinical-morphological-and-genetic-characterization-and-implications-for-targeted-treatment
#20
Simon Andreasen, Morten Grauslund, Steffen Heegaard
PURPOSE: Ductal carcinomas (DCs) of the lacrimal gland are very rare but aggressive malignancies. We investigated DC of the lacrimal gland for potentially clinically actionable targets in the search for new therapeutic options. METHODS: Case 1: A 77-year-old man, presented with diplopia and xerophtalmia; case 2: A 53-year-old man, presented with headache, proptosis and chemosis and case 3: A 73-year-old man, presenting with chemosis and a corneal abscess. All three cases were characterized morphologically including immunohistochemistry and genetically with fluorescence in situ hybridization (FISH) and one case with next-generation sequencing (NGS) of cancer relevant genes...
November 3, 2016: Acta Ophthalmologica
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